HHV-6 and HHV-8

• Human Herpes Virus 6 and 8 (HHV-6 and HHV-8) are double stranded linear DNA viruses.

HHV-6

• Belongs to the Herpesviridae family, subfamily Betaherpesvirinae, genus Roseolovirus.
• It transmits through respiratory secretions.
• The virus attaches to dendritic cells, which present antigens to T cells.
• The virus migrates to lymph nodes, infecting CD4+ T lymphocytes where it replicates efficiently.
• HHV-6 undergoes the lytic cycle within T cells, producing new viruses that destroy the cell and infect neighboring cells.
• It can also replicate in monocytes, macrophages, NK cells, astrocytes, megakaryocytes, and glial cells, but less efficiently.
• HHV-6 enters a latent state in monocytes, potentially reactivating in immunocompromised individuals, and may cause encephalitis.
• Primary infection causes roseola infantum (exanthem subitum or sixth disease).
• Roseola infantum commonly occurs in children aged 6 months to 2 years.
• Incubation period for Roseola infantum is 1-2 weeks.
• Symptoms of Roseola infantum include high fever (up to 40°C or 104°F) lasting 3-5 days, peri-orbital edema, acute otitis media, rhinorrhea, cough, vomiting, diarrhea, bulging fontanelle, lymphadenopathy, and Nagayama spots.
• Nagayama spots are erythematous papules that appear on the soft palate and uvula.
• After fever subsides, a maculopapular rash appears on the neck, trunk, face, and extremities, lasting a few hours to two days.
• Diagnosis involves clinical findings, PCR to identify viral DNA, and serological tests for IgG antibodies against HHV-6.
• Treatment includes supportive care (antipyretics, increased fluid intake).
• Antivirals like acyclovir or ganciclovir can be used in severe cases (immunocompromised individuals).

HHV-8

• HHV-8 is also called Kaposi's sarcoma-associated herpesvirus (KSHV).
• It belongs to the family of human gammaherpesviruses.
• HHV-8 is one of the seven known oncoviruses, specifically causing Kaposi's sarcoma (KS).
• It is a large, double-stranded linear DNA virus.
• The virus is surrounded by an icosahedral capsid, a protein layer called the tegument, and an envelope with viral glycoproteins.
• HHV-8 transmits through sexual contact.
• The virus enters B cells, endothelial cells, macrophages, and epithelial cells.
• In the latent phase, the virus remains in the cell without destroying it and expresses the latency-associated nuclear antigen (LANA-1).
• LANA-1 inhibits tumor suppressor protein p53, preventing apoptosis, leading to uncontrolled cellular proliferation.
• During the lytic phase, the virus replicates, producing new viruses that destroy the cell and infect neighboring cells.
• Infection is rare in individuals with healthy immune systems due to humoral (antibodies) and cellular (cytotoxic T cells) immune responses.
• Immunocompromised individuals are at higher risk.
• Clinical presentation of Kaposi’s sarcoma has four types: classic, endemic, epidemic (AIDS-associated), and immunosuppression therapy-related.
• Kaposi’s sarcoma is characterized by vascular proliferation and dark or violaceous plaques on the skin, mouth, GI tract, or lungs.
• Other symptoms include red or purple skin lesions resembling bruises, which can grow into nodules and merge, weight loss, nausea, vomiting, diarrhea, bleeding, malabsorption, shortness of breath, chest pain, cough, and hemoptysis.
• Diagnosis involves biopsy of lesions, microscopic examination showing spindle cells, immunohistochemical staining for LANA-1, and PCR for viral DNA.
• Treatment aims to stop the progression of KS.
• Local treatments include radiation therapy and cryosurgery for skin lesions.
• Chemotherapy (doxorubicin, daunorubicin, thalidomide, paclitaxel) is used for widespread disease.