Herpesvírus Humano 8

Classificação

Características Gerais e Epidemiologia

Características gerais do herpesvírus humano 8 (HHV-8)

• Também conhecido como herpesvírus associado ao sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions
• Taxonomia:
  • Família: Herpesviridae Herpesviridae A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. Subfamilies, based on biological characteristics, include: alphaherpesvirinae; betaherpesvirinae; and gammaherpesvirinae. Herpes Simplex Virus 1 and 2
  • Subfamília: Gammaherpesvirinae Gammaherpesvirinae A subfamily of herpesviridae characterized by variable reproductive cycles. The genera include: lymphocryptovirus and rhadinovirus. Epstein-Barr Virus
  • Género: Radinovírus
• Vírus DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure:
  • Cadeia dupla
  • Linear
• Estrutura:
  • Núcleo de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
  • Constituído por uma cápside icosaédrica
  • Tegumento
  • Envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology lipídico com glicoproteínas “spike”

Doenças associadas

• Sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions ( tumor Tumor Inflammation maligno vascular)
• Doença multicêntrica de Castleman (doença linfoproliferativa de células B)
• Linfomas primários de efusão (linfoma não Hodgkin)

Epidemiologia

• Os tumores associados ao HHV-8 representam <1% de todos os cancros a nível mundial.
• Idade: o risco de sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions aumenta com o declínio da imunidade celular em indivíduos mais MAIS Androgen Insensitivity Syndrome velhos.
• Mais MAIS Androgen Insensitivity Syndrome comum:
  • Região mediterrânica
  • África Subsariana (endémica)
• Homens > mulheres, sobretudo em homens que fazem sexo com homens

Patogénese

Reservatório

Os humanos são o único reservatório conhecido.

Transmissão

O mecanismo de transmissão do vírus ainda não está totalmente esclarecido.

• Segundo a evidência atual ocorre sobretudo através de:
  • Saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy
  • Contacto sexual
• Estão descritos alguns casos de transmissão por transplante de sangue e órgãos sólidos.

Fatores de risco do hospedeiro

A infeção pelo herpesvírus humano 8 é maioritariamente assintomática. As manifestações clínicas podem ocorrer em pacientes imunodeprimidos:

• VIH/SIDA (o sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions é uma condição definidora de SIDA)
• Pacientes transplantados

Ciclo de replicação viral

• Processo:
  • O vírus liga-se às células hospedeiras com glicoproteínas de superfície → entrada
  • Pode levar a:
    • Fase de latência → produção de proteínas que promovem a oncogénese
    • Fase de replicação lítica
• Infeta:
  • Células epiteliais
  • Células endoteliais
  • Linfócitos
• A latência ocorre em:
  • Linfócitos B
  • Células endoteliais vasculares

Fisiopatologia

• O vírus é transmitido pela saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy → replica-se nas células epiteliais da orofaringe
• Leva à infeção de células B e células endoteliais → pode ocorrer latência viral
• A infeção é controlada pelo sistema imune.
• Se o paciente ficar imunodeprimido → reativação do vírus latente → mais MAIS Androgen Insensitivity Syndrome células são infetadas
• As proteínas virais interagem com as vias celulares, atuando através do/a:
  • ↑ Atividade do fator de crescimento celular → proliferação
  • Inibição de genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure de supressão tumoral → previne a apoptose
• Isto pode potenciar a:
  • Angiogénese
  • Oncogénese

Doenças Causadas por HHV-8

Comparação de Herpesvírus

A tabela abaixo compara os 9 herpesvírus considerados endémicos em humanos; existem 115 espécies diferentes de herpesvírus no total, agrupadas em 3 famílias:

• Alfa (infeta células epiteliais e produz infeção latente em neurónios pós-mitóticos)
• Beta (infetar e produz infeção latente em vários tipos de células)
• Gama (produz infeção latente, sobretudo em células linfóides)