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Kaposi's sarcoma (KS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8). KS is an AIDS-defining cancer, and it is changing in the post-antiretroviral therapy (post-ART) era. In countries with ready access to ART, approximately one-third of KS cases present in patients with undetectable HIV loads and CD4 counts of ≥200 cells/µl. This is in contrast to pre-ART era KS, which was associated with systemic HIV replication and CD4 counts of ≤200 cells/µl. Using primary patient biopsy specimens, we identified a novel molecular signature that characterizes AIDS KS lesions that develop in HIV-suppressed patients on ART: KSHV transcription is limited in HIV-suppressed patients. With one exception, only the canonical viral latency mRNAs were detectable. In contrast, early AIDS KS lesions expressed many more viral mRNAs, including, for instance, the viral G protein-coupled receptor (vGPCR).

Restricted Kaposi’s Sarcoma (KS) Herpesvirus Transcription in KS Lesions from Patients on Successful Antiretroviral Therapy