Kaposi Sarcoma-Associated Herpesvirus Sequencing in People Living With HIV in the Southern United States Reveals Subtype Diversity and Multiple Infections

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and lymphoproliferative diseases collectively identified as KSHV-associated diseases (KAD). While KAD incidence has decreased across the United States, regional and population-based variability exists, with higher rates in southern states. To understand the molecular epidemiology of KSHV in this region, samples were collected from people living with HIV (PWH) with or without history of KAD. PWH, mainly men who have sex with men (MSM), were recruited from a large, urban hospital system in Dallas, Texas, in two separate studies. The studies included 220 individuals without KAD and 59 patients with KAD. Whole blood and/or oral fluids were collected and tested by qPCR. KSHV subtypes were determined from 66 of 85 individuals with detectable KSHV loads by a combination of next-generation and targeted Sanger sequencing. All major KSHV subtypes, except D, were observed including subtypes E and F. In each of three individuals, multiple KSHV genome variants were identified. This study importantly highlights KSHV subtype diversity in the southern United States, which is an area with a high KS incidence. Genome diversity and multiple infections merit epidemiological consideration, including for the future development of vaccines.

Keywords: Kaposi's sarcoma associated herpesvirus (KSHV); human herpesvirus 8 (HHV8); multiple infections; viral subtypes; whole viral sequencing.