Viral profiling identifies multiple subtypes of Kaposi's sarcoma.

Area of Science:

• Oncology
• Virology
• Infectious Diseases

Background:

• Kaposi's sarcoma (KS) is the most common cancer in HIV-infected individuals.
• KS is caused by the KS-associated herpesvirus (KSHV).
• KSHV is endemic in Malawi, a region with a high prevalence of HIV and KS.

Purpose of the Study:

• To investigate KSHV transcription profiles in treatment-naive HIV-infected patients with KS.
• To identify potential subtypes of KS lesions based on viral gene expression.
• To explore therapeutic targets for KS based on viral transcription patterns.

Main Methods:

• Cross-sectional study of 70 HIV-infected patients with KS and no prior therapy.
• Analysis of plasma and biopsy samples using a novel KSHV real-time quantitative PCR (qPCR) array.
• Examination of KSHV mRNA transcription across the viral genome, focusing on latency and lytic genes.

Main Results:

• 89% of patients had detectable KSHV in plasma.
• Two distinct KS lesion subtypes were identified based on KSHV transcription.
• Subtype 1: lesions transcribing viral RNAs across the genome.
• Subtype 2: lesions with limited transcription restricted to the latency locus.
• Latency locus genes (LANA, vCyc, vFLIP, kaposin, miRNAs) and K15 mRNA were abundantly transcribed in most samples.

Conclusions:

• This study demonstrates for the first time the existence of multiple subtypes of KS lesions in treatment-naive patients.
• These subtypes exhibit differential KSHV transcription patterns.
• The identification of specific viral gene transcription offers potential targets for antiviral therapies, such as ganciclovir or AZT, in addition to chemotherapy.