New Kaposi's sarcoma-associated herpesvirus variant in men who have sex with men 3 associated with severe pathologies Running title: New KSHV variant identified in MSM

BackgroundKaposi sarcoma (KS)–associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France.MethodsThe study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)–infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant.ResultsWe found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups.ConclusionsSubtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.