K — Kaposi Sarcoma–Associated Herpesvirus (KSHV / HHV-8)
Kaposi sarcoma–associated herpesvirus (KSHV) is a gammaherpesvirus with a large double-stranded DNA genome that establishes lifelong latency, primarily in endothelial cells and B lymphocytes. Like other herpesviruses, KSHV alternates between latent and lytic replication cycles. During latency, only a restricted subset of viral genes is expressed, including latency-associated nuclear antigen (LANA), vCyclin, and vFLIP.
LANA tethers the viral episome to host chromosomes, ensuring persistence during cell division. vCyclin and vFLIP dysregulate cell cycle control and activate NF-κB signaling, promoting cell survival and proliferation. KSHV also encodes homologs of human cytokines and signaling molecules, including viral IL-6, which contributes to inflammation and angiogenesis.
Pathogenesis is tightly linked to immune suppression. In individuals with impaired immunity (e.g., advanced HIV infection), viral reactivation and proliferation of infected endothelial cells lead to Kaposi sarcoma, a vascular tumor characterized by spindle cells and abnormal angiogenesis. KSHV is also associated with primary effusion lymphoma and multicentric Castleman disease.
KSHV illustrates viral oncogenesis driven by persistent latency, immune evasion, and manipulation of host signaling pathways. Research focuses on latency control mechanisms, viral microRNAs, interactions with HIV co-infection, and targeted therapies against NF-κB and angiogenic pathways.
Kaposi sarcoma–associated herpesvirus (KSHV) is a gammaherpesvirus with a large double-stranded DNA genome that establishes lifelong latency, primarily in endothelial cells and B lymphocytes. Like other herpesviruses, KSHV alternates between latent and lytic replication cycles. During latency, only a restricted subset of viral genes is expressed, including latency-associated nuclear antigen (LANA), vCyclin, and vFLIP.
LANA tethers the viral episome to host chromosomes, ensuring persistence during cell division. vCyclin and vFLIP dysregulate cell cycle control and activate NF-κB signaling, promoting cell survival and proliferation. KSHV also encodes homologs of human cytokines and signaling molecules, including viral IL-6, which contributes to inflammation and angiogenesis.
Pathogenesis is tightly linked to immune suppression. In individuals with impaired immunity (e.g., advanced HIV infection), viral reactivation and proliferation of infected endothelial cells lead to Kaposi sarcoma, a vascular tumor characterized by spindle cells and abnormal angiogenesis. KSHV is also associated with primary effusion lymphoma and multicentric Castleman disease.
KSHV illustrates viral oncogenesis driven by persistent latency, immune evasion, and manipulation of host signaling pathways. Research focuses on latency control mechanisms, viral microRNAs, interactions with HIV co-infection, and targeted therapies against NF-κB and angiogenic pathways.