Classification
Identification of DNA viruses:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. Viruses with a DNA genome can be further characterized as single or double stranded. “Enveloped” viruses are covered by a thin coat of cell membrane, which is usually taken from the host cell. If the coat is absent, however, the viruses are called “naked” viruses. Some enveloped viruses translate DNA into RNA before incorporating into the genome of the host cell.
General Characteristics and Epidemiology
General features of human herpesvirus 8 (HHV-8)
- Also known as Kaposi sarcoma–associated herpesvirus
- Taxonomy:
- Family: Herpesviridae
- Subfamily: Gammaherpesvirinae
- Genus: Rhadinovirus
- DNA virus:
- Double-stranded
- Linear
- Structure:
- DNA core
- Icosahedral nucleocapsid
- Tegument
- Lipid envelope with glycoprotein spikes
Associated diseases
- Kaposi sarcoma (vascular malignancy)
- Multicentric Castleman disease (B-cell lymphoproliferative disease)
- Primary effusion lymphomas (a non-Hodgkin lymphoma)
Epidemiology
- Global prevalence: 2%–10%
- More common in:
- Mediterranean region
- Sub-Saharan Africa (endemic)
- Men > women, particularly men who have sex with men
Pathogenesis
Reservoir
Humans are the only known reservoir.
Transmission
It is not entirely clear how the virus is transmitted.
- Appears to mainly be through:
- Saliva
- Sexual contact
- Transmission through blood and solid organ transplantation has been documented.
Host risk factors
Human herpesvirus 8 infection is usually asymptomatic. Clinical manifestations can occur in immunocompromised patients:
- HIV/AIDS (Kaposi sarcoma is an AIDS-defining condition)
- Transplant patients
Viral replication cycle
- Process:
- Virus attaches to host cells with surface glycoproteins → entry
- Can either lead to:
- Latency → produce proteins that promote oncogenesis
- Lytic replication
- Infects:
- Epithelial cells
- Endothelial cells
- Lymphocytes
- Latency occurs in:
- B lymphocytes
- Vascular endothelial cells
Pathophysiology
- Virus is transmitted through saliva → replicates in epithelial cells in the oropharynx
- Leads to infection of B cells and endothelial cells → viral latency may occur
- Infection is kept in check by the immune system.
- If the patient becomes immunocompromised → reactivation of latent virus → more cells are infected
- Viral proteins interact with cellular pathways, including:
- ↑ Cellular growth factor activity → proliferation
- Inhibition of tumor suppression genes → prevents apoptosis
- This can lead to:
- Angiogenesis
- Oncogenesis
Diseases Caused by HHV-8
| Disease | Clinical presentation | Diagnosis | Management |
|---|---|---|---|
| Kaposi sarcoma | Malignant vascular lesions of the:
| Biopsy of lesions |
|
| Multicentric Castleman disease |
|
|
|
| Primary effusion lymphomas | Manifestations depend on the site of fluid accumulation:
|
|
|
Comparison of Herpesviruses
The following table compares the 9 herpesviruses considered endemic in humans; there are 115 different known species of herpesviruses, grouped into 3 families:
- Alpha (infect epithelial cells and produce latent infection in postmitotic neurons)
- Beta (infect and produce latent infection in a variety of cell types)
- Gamma (produce latent infection, mainly in lymphoid cells)
| HHV | Common name | Primary target cells | Latency site | Clinical presentation* |
|---|---|---|---|---|
| 1 (alpha group) | HSV-1 | Mucoepithelial cells | Dorsal root ganglia |
|
| 2 (alpha group) | HSV-2 |
| ||
| 3 (alpha group) | VZV |
| ||
| 4 (gamma group) | EBV |
| Memory B cells |
|
| 5 (beta group) | CMV |
| Hematopoietic progenitor cells in bone marrow |
|
| 6A, 6B (beta group) | HHV-6 | T cells | Monocytes | Roseola |
| 7 (beta group) | HHV-7 | T cells | ||
| 8 (gamma group) | Kaposi sarcoma–associated herpesvirus |
| B cells | Kaposi sarcoma |
References
- Mui UN, Haley CT, Tyring SK. (2017). Viral oncology: molecular biology and pathogenesis. J Clin Med 6(12). https://pubmed.ncbi.nlm.nih.gov/29186062/
- Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. (2019). Kaposi sarcoma. Nat Rev Dis Primers 5(1):9. https://pubmed.ncbi.nlm.nih.gov/30705286/
- Yan L, Majerciak V, Zheng ZM, Lan K. (2019). Towards better understanding of KSHV life cycle: from transcription and posttranscriptional regulations to pathogenesis. Virol Sin; 34(2):135-161. https://pubmed.ncbi.nlm.nih.gov/31025296/
- Dittmer DP, Damania B. (2016). Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J Clin Invest 126:3165–3175. https://pubmed.ncbi.nlm.nih.gov/27584730/
- Jha HC, Banerjee S, Robertson ES. (2016). The role of gammaherpesviruses in cancer pathogenesis. Pathogens 5(1). https://pubmed.ncbi.nlm.nih.gov/26861404/
- Damania B, Münz C. (2019). Immunodeficiencies that predispose to pathologies by human oncogenic γ-herpesviruses. FEMS Microbiol Rev 43:181–192. https://pubmed.ncbi.nlm.nih.gov/30649299/
- Purushothaman P, Uppal T, Sarkar R, Verma SC. (2016). KSHV-mediated angiogenesis in tumor progression. Viruses 8(7). https://pubmed.ncbi.nlm.nih.gov/27447661/
- Wen KW, Damania B. (2010). Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett 289(2):140-50. https://pubmed.ncbi.nlm.nih.gov/19651473/
- Gonçalves PH, Uldrick TS, Yarchoan R. (2017). HIV-associated Kaposi sarcoma and related diseases. AIDS 31:1903–1916. https://pubmed.ncbi.nlm.nih.gov/28609402/
- Schneider JW, Dittmer DP. (2017). Diagnosis and treatment of Kaposi sarcoma. Am J Clin Dermatol 18:529–539. https://pubmed.ncbi.nlm.nih.gov/28324233/
- Centers for Disease Control and Prevention. (1981). Follow-up on Kaposi’s sarcoma and pneumocystis pneumonia. MMWR 30:409–410.
- Rewane A, Tadi P. (2021). Herpes virus type 8. StatPearls. Retrieved June 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK556023/
- Casper C. (2020). Disease associations of human herpesvirus 8 infection. In Bloom A (Ed.), UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/disease-associations-of-human-herpesvirus-8-infection
- Casper C. (2020). Virology, epidemiology, and transmission of human herpesvirus 8 infection. In Bloom A (Ed.), UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/virology-epidemiology-and-transmission-of-human-herpesvirus-8-infection
