Lymphocytic Choriomeningitis Virus

Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus transmitted to humans via rodents, the primary reservoir. Viral infections can occur through direct contact (such as through a break in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin) with rodent urine, saliva, or droppings or via inhalation of aerosolized virus. Vertical transmission and, rarely, organ transplantation Organ Transplantation Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Organ Transplantation also lead to infections. The disease typically results in a self-limited, febrile, biphasic disease. In severe cases, patients can present with encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, or meningoencephalitis. Lymphocytic choriomeningitis virus infections of pregnant women have also been recognized as a significant teratogen resulting in fetal death or congenital defects. Diagnosis is by serology or RT-PCR. Management is supportive.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Classification

Rna viruses flowchart classification

RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure genome viruses can be further characterized by either a single- or double-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. “Enveloped” viruses are covered by a thin coat of cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase, a viral enzyme, to transcribe their genome into messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Basic features of lymphocytic choriomeningitis virus (LCMV)

  • Enveloped
  • Spherical
  • Midsize (diameter between 60 and 300 nm)
  • 2 viral surface glycoproteins on envelope: G1 and G2
  • Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview genome:
    • Encapsulated by a helical nucleocapsid
    • Segmented with:
      • A large (L) single-stranded, negative-sense RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure  
      • A small (S) ambisense RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure
    • Carries RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure-dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase (RDRP)

Taxonomy:

  • Family Arenaviridae
  • Genus Mammarenavirus
  • Viruses contain host ribosomes, giving the virus a granular appearance (arenosus is Latin for “sandy”)
  • Other arenaviruses include:
    • Lassa virus Lassa Virus Lassa virus, part of the Arenaviridae family, is an ssRNA virus that causes Lassa fever, a type of viral hemorrhagic illness. The virus is endemic in parts of West Africa (Sierra Leone, Liberia, Guinea, and Nigeria) and neighboring countries. The reservoir is the multimammate rat (Mastomys natalensis), and transmission is via inhalation or contact with rodent excretions or consumption of rodents. Lassa Virus (Lassa fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Junin virus (Argentine hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Machupo virus (Bolivian hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Guanarito virus (Venezuelan hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Sabia (Brazilian hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Chapare (Chapare hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
    • Lujo (Lujo hemorrhagic fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
Electron micrograph of lymphocytic choriomeningitis virus

Electron micrograph of lymphocytic choriomeningitis virus

Image: “Negative stain electron micrograph of an arenavirus from a mouse that tested positive for LCM” by CDC. License: Public Domain

Epidemiology

  • Seroprevalence in the United States: approximately 5%
  • Disease found in:
    • North and South America
    • Europe
    • Australia
    • Japan
  • No racial or sexual predilection
  • Infections more common in young adults
  • Infections are more common in the fall and winter (when rodents seek shelter indoors).

Pathogenesis

Reservoir

Arenaviruses: cause chronic infections in rodents (house mouse, Mus musculus)

Transmission

  • Direct contact with material contaminated by feces/urine/saliva of infected rodents (through the eye, nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose, mouth, a break in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, or animal bite) 
  • Inhalation of aerosolized virus 
  • Vertical transmission from mother to fetus
  • Organ transplantation (recipient of infected donor tissue)

Life cycle

  1. Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview attaches to host receptors through envelope glycoproteins. 
  2. Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview is subsequently endocytosed, thus gaining entry into the cell. 
  3. Viral fusion with an endosome follows. 
  4. The virus merges with the endosome membrane, allowing the release of the viral ribonucleocapsid into the cytoplasm. 
  5. The RDRP mediates the viral gene replication and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription in the cytoplasm of the host. 
  6. New virions are assembled and budding occurs, releasing the virion to infect other cells. 
Life cycle of lymphocytic choriomeningitis virus

Life cycle of lymphocytic choriomeningitis virus:
1: Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview attaches to host receptors through envelope glycoproteins.
2: Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview is subsequently endocytosed, thus gaining entry into the cell.
3: Viral fusion with an endosome follows.
4: The virus fuses with the endosome membrane, allowing release of the viral ribonucleocapsid (vRNP) into the cytoplasm.
5: The RDRP mediates the viral gene replication and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription in the host cytoplasm.
6: New virions are assembled and budding occurs, releasing the virion to infect other cells.

Image: “Arenavirus life cycle” by Y Liang et al. License: CC BY 4.0

Host risk factors

  • Owners of pet mice or hamsters
  • Laboratory workers

Disease process

LCMV is not cytotoxic, but while the host immune response tries to eliminate the virus, this may also trigger immune-mediated disease. The immune response produces the different manifestations of the disease.

  • Incubation period: up to 13 days
  • Primary viremia ensues → dissemination to other organs
  • The virus reaches the CNS ( meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges, choroid plexus, and ventricular ependymal lining), leading to infiltration of inflammatory cells.

Clinical Presentation

Acquired lymphocytic choriomeningitis virus infection

Infection with LCMV results in a biphasic illness.

Symptom onset:

  • Occurs 8–13 days after exposure
  • 1st symptoms may last 5–7 days.
  • 33% are asymptomatic.
  • 50% have febrile illness without neurologic involvement.

1st-phase symptoms:

  • Fever
  • Lack of appetite
  • Headache
  • Muscle aches
  • Malaise
  • Nausea and/or vomiting
  • Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
  • Maculopapular rash

2nd-phase symptoms:

Following a few days of recovery, 2nd-phase symptoms may start, which include neurologic symptoms (typical of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis and/or encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis).

  • Increased headache, photophobia
  • Nuchal rigidity
  • Change in mental status (lethargy, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma)

Other less frequent findings:

  • Orchitis Orchitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis
  • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Arthritis
  • Parotitis
  • Pneumonitis

Congenital lymphocytic choriomeningitis virus infection

Women who become infected with LCMV during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care can pass the infection to the fetus.

  • Infections occurring during the 1st trimester may result in fetal death or spontaneous abortion Spontaneous abortion Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks' gestation. However, the layperson use of the term "abortion" is often intended to refer to induced termination of a pregnancy, whereas "miscarriage" is preferred for spontaneous loss. Spontaneous Abortion.
  • Infections in the 2nd and 3rd trimesters can result in birth defects, including:
    • Blindness: Chorioretinitis Chorioretinitis Chorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis is a common finding in children.
    • Developmental delay
    • Hydrocephalus 
    • Epilepsy Epilepsy Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Epilepsy

Organ transplant lymphocytic choriomeningitis virus infection

Significant immunosuppression in transplant recipients play a role in the development of disease:

  • Encephalopathy
  • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
  • Renal/hepatic impairment
  • Graft dysfunction
  • Coagulopathy
  • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Fever

Diagnosis

Diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests

  • Confirmatory tests for the LCMV include:
    • Detecting IgM and IgG antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins in the CSF and serum
    • RT-PCR
    • CSF viral culture
  • For congenital LCMV infection, babies may not have the virus anymore, so IgM and IgG levels are used.
  • Common findings in the CSF include:
    • Increase in protein levels
    • Lymphocytic pleocytosis
    • Decrease in the glucose levels

Additional findings

During the 1st phase of the disease, the most common laboratory abnormalities are

  • CBC:
    • Leukopenia
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes

Management

  • Patients with aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, or meningoencephalitis require: 
    • Hospitalization
    • Supportive treatment based on severity
  • Recovery generally takes up to 3 weeks.
  • Mortality rate:
    • Acquired LCMV infection: approximately 1%
    • Congenital LCMV infection: can reach 35% depending on the associated disorders

Comparison of Species

Arenaviruses can cause neurologic disease (LCMV) and/or hemorrhagic fevers, for which one of the major etiologies is the Lassa virus Lassa Virus Lassa virus, part of the Arenaviridae family, is an ssRNA virus that causes Lassa fever, a type of viral hemorrhagic illness. The virus is endemic in parts of West Africa (Sierra Leone, Liberia, Guinea, and Nigeria) and neighboring countries. The reservoir is the multimammate rat (Mastomys natalensis), and transmission is via inhalation or contact with rodent excretions or consumption of rodents. Lassa Virus.

Table: Comparison of lymphocytic choriomeningitis virus (LCMV) and Lassa virus Lassa Virus Lassa virus, part of the Arenaviridae family, is an ssRNA virus that causes Lassa fever, a type of viral hemorrhagic illness. The virus is endemic in parts of West Africa (Sierra Leone, Liberia, Guinea, and Nigeria) and neighboring countries. The reservoir is the multimammate rat (Mastomys natalensis), and transmission is via inhalation or contact with rodent excretions or consumption of rodents. Lassa Virus
Organism LCMV Lassa virus Lassa Virus Lassa virus, part of the Arenaviridae family, is an ssRNA virus that causes Lassa fever, a type of viral hemorrhagic illness. The virus is endemic in parts of West Africa (Sierra Leone, Liberia, Guinea, and Nigeria) and neighboring countries. The reservoir is the multimammate rat (Mastomys natalensis), and transmission is via inhalation or contact with rodent excretions or consumption of rodents. Lassa Virus
Family Arenaviridae
Genus Mammarenavirus
Characteristics
  • Enveloped
  • Midsize
  • Spherical
  • Segmented genome
  • Single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure (ssRNA)
  • Enveloped
  • Midsize
  • Spherical
  • Segmented genome
  • ssRNA
Reservoir Rodents
Transmission
  • Aerosols
  • Direct contact
  • Vertical transmission
  • Organ transplantation
  • Aerosols
  • Direct contact
  • Ingestion
  • Person to person (through exposure to blood, secretions, tissue of infected individual)
Clinical course Biphasic:
  • Flu-like illness
  • Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Majority of cases asymptomatic or only mild symptoms
  • Hemorrhagic manifestations
  • Deafness is common.
Diagnosis
  • Serology
  • RT-PCR
Management Supportive
  • Supportive
  • Ribavirin
Prevention Avoid contact with rodents and their body fluids.
  • Avoid contact with rodents and their body fluids.
  • Personal protective equipment

Differential Diagnosis

The following selected RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure viruses can also lead to CNS infection. 

  • Tick-borne encephalitis virus Tick-borne Encephalitis Virus Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus: due to a single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus of the genus Flavivirus. Transmission primarily occurs via Ixodes ticks found in Europe, Russia, and Asia. Most patients are asymptomatic, but symptomatic individuals may experience a biphasic illness. Patients can develop neurologic manifestations, such as meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, or meningoencephalitis. Serology or PCR can confirm the diagnosis. There is no effective antiviral therapy for tick-borne encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis virus infections, so management is supportive
  • Equine encephalitis viruses Equine Encephalitis Viruses Equine encephalitis viruses (EEVs), belonging to the Togaviridae family and Alphavirus genus, are mosquito-borne arboviruses that infect humans and cause minor illness or, in severe cases, encephalitis. The eastern equine encephalitis (EEE) virus complex consists of the EEE virus, Madariaga virus, western EEV, and Venezuelan EEV. Equine Encephalitis Viruses: mosquito-borne arboviruses (belonging to Togaviridae, genus Alphavirus) that can cause minor viral illness and, in severe cases, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis in humans. The virus is a positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. The eastern equine encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis virus is the most clinically relevant in the United States. The virus is maintained in a cycle between mosquito and often avian hosts but spreads to humans via bridge vectors. Symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache, and vomiting, with the majority of patients recovering. The illness can progress to severe encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis. Diagnosis is by CSF studies, with serology and virus antigen or genomic sequence detection. There is no specific treatment, and therapy is largely supportive.
  • West Nile Virus West Nile Virus West Nile virus is an enveloped, positive-sense, single-stranded RNA virus of the genus Flavivirus. Birds are the primary hosts and the disease is most often transmitted by Culex mosquitoes. Most people infected with West Nile virus are asymptomatic. Some patients develop West Nile fever (a self-limited, febrile illness) and a very small proportion of patients develop West Nile neuroinvasive disease. West Nile Virus: can cause neuroinvasive disease, including meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, and acute flaccid paralysis. The virus is an enveloped, positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus of the genus Flavivirus. The primary hosts are birds, and the disease is most often transmitted by Culex mosquitoes. Most people infected with the virus are asymptomatic. Some patients will have a self-limited febrile illness, termed West Nile fever West Nile fever West Nile virus is an enveloped, positive-sense, single-stranded RNA virus of the genus Flavivirus. Most people infected with West Nile virus are asymptomatic. Some patients develop West Nile fever (a self-limited, febrile illness) and a very small proportion of patients develop West Nile neuroinvasive disease. West Nile Virus. The diagnosis is confirmed with serum or CSF serology or RT-PCR. Management is generally supportive. Prevention is aimed at local mosquito control and protection from mosquito bites. 
  • Saint Louis encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis virus: enveloped, positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus belonging to the genus Flavivirus and causing St. Louis encephalitis St. Louis Encephalitis The Saint Louis encephalitis virus (SLEV) is a member of the genus Flavivirus and is the cause of St. Louis encephalitis. This small, enveloped, positive-sense, single-stranded RNA virus is transmitted by Culex mosquito species. Most infections are asymptomatic. Symptomatic individuals may have varied presentations, with flu-like symptoms, aseptic meningitis, encephalitis, or meningoencephalitis. St. Louis Encephalitis Virus. Transmission is by Culex mosquito species. Most infections are asymptomatic. Symptomatic individuals may have flu-like symptoms, aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, or meningoencephalitis. The diagnosis is confirmed with serology. There is no effective antiviral treatment, so management is supportive. Prevention is aimed at local mosquito control and personal protection with insect repellent and protective clothing. 

References:

  1. Bonthius D.J. (2012). Lymphocytic choriomeningitis virus: an underrecognized cause of neurologic disease in the fetus, child, and adult. Seminars in Pediatric Neurology 19:89–95. https://doi.org/10.1016/j.spen.2012.02.002
  2. Centers for Disease Control and Prevention. (2013). Viral hemorrhagic fevers. Retrieved May 20, 2021, from https://www.cdc.gov/vhf/virus-families/arenaviridae.html
  3. Centers for Disease Control and Prevention (2008). Brief report: Lymphocytic choriomeningitis virus transmitted through solid organ transplantation. MMWR Morb Mortal Wkly Rep 57:799–801.
  4. Centers for Disease Control and Prevention. (2014). Lassa fever. https://www.cdc.gov/vhf/lassa/symptoms/index.html
  5. Emonet, S., Retornaz, K., Gonzalez, J.P., de Lamballerie, X., Charrel, R.N. (2007). Mouse-to-human transmission of variant lymphocytic choriomeningitis virus. Emerg Infect Dis 13:472–475. https://doi.org/10.3201/eid1303.061141
  6. McDonald, P., Chandrasekar, P. (2017). Lymphocytic choriomeningitis virus (LCMV) infection. Medscape. Retrieved May 20, 2021, from https://emedicine.medscape.com/article/220796-overview
  7. Ryan K.J. (2017). Arthropod-borne and other zoonotic viruses. Chapter 16 of Sherris Medical Microbiology, 7th ed. https://accessmedicine.mhmedical.com/content.aspx?bookid=2268&sectionid=176083946
  8. Shao, J., Liang, Y., Ly, H. (2015). Human hemorrhagic fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis. Pathogens 4:283–306. https://doi.org/10.3390/pathogens4020283

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