Abstract
Within the Pumwani sex worker cohort, a subgroup remains seronegative, despite frequent exposure to HIV-1; some of them seroconverted several years later. This study attempts to identify viral variations in 5′LTR-leader sequences (5′LTR-LS) that might contribute to the late seroconversion. The 5′LTR-LS contains sites essential for replication and genome packaging, viz, primer binding site (PBS), major splice donor (SD), and major packaging signal (PS). The 5′LTR-LS of 20 late seroconverters (LSC) and 122 early seroconverters (EC) were amplified, cloned, and sequenced. HelixTree 6.4.3 was employed to classify HIV subtypes and sequence variants based on seroconversion status. We find that HIV-1 subtypes A1.UG and D.UG were overrepresented in the viruses infecting the LSC (P < 0.0001). Specific variants of PBS (Pc < 0.0001), SD1 (Pc < 0.0001), and PS (Pc < 0.0001) were present only in the viral population from EC or LSC. Combinations of PBS [PBS-2 (Pc < 0.0001) and PBS-3 (Pc < 0.0001)] variants with specific SD sequences were only seen in LSC or EC. Combinations of A1.KE or D with specific PBS and SD variants were only present in LSC or EC (Pc < 0.0001). Furthermore, PBS variants only present in LSC co-clustered with PBS references utilizing tRNAArg; whereas, the PBS variants identified only in EC co-clustered with PBS references using tRNALys,3 and its variants. This is the first report that specific PBS, SD1, and PS sequence variants within 5′LTR-LS are associated with HIV-1 seroconversion, and it could aid designing effective anti-HIV strategies.
Highlights
In 2016, there were 62,000 new HIV infections, and 1,600,000 people living with HIV in Kenya [1].Efforts are underway, globally, to find ways to prevent infection, as well as to explore practical cures for HIV [2,3]
We examined whether specific sequences of primer binding site (PBS), splice donor (SD), and packaging signal (PS), and their combinations, are more likely to be associated with HIV viral population in late seroconverters
HIV-1 late seroconversion has been observed in Pumwani sex worker cohort
Summary
In 2016, there were 62,000 new HIV infections, and 1,600,000 people living with HIV in Kenya [1]. To find ways to prevent infection, as well as to explore practical cures for HIV [2,3]. The most at-risk individuals for infection by HIV are commercial sex workers (CSW), intravenous drug users, and men who have sex with men (MSM). The CSW population is at increased risk, as they may have hundreds of sexual partners each year. Compounding the risk of infection and transmission, many of them could be intravenous drug users, and/or may be infected with other sexually transmitted pathogens that could enhance HIV transmission [4].
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