Transmitted/founder (T/F) HIV-1 derived from sexual contact exhibits greater transmission fitness in human cervical tissue than T/F HIV-1 from blood-to-blood contact: Unique glycan profiles on T/F envelopes associated with transmission phenotypes

• DOI: 10.1371/journal.ppat.1013177
• Publication Date: 2025-05-23T18:00:08Z
• Authors: Yiying Zhang; Katja Klein; Annette Ratcliff; Sashini Loku Gala...; Nicholas Hathaway; Nicholas Twells; Mukti Patel; Stephen Temesy; Jeffrey A. Bailey; Lara K. Mahal; Carole Creuzenet; Eric J. Arts
• Keywords: Ex vivo; Sexual transmission

Human immunodeficiency virus 1 (HIV-1) risk groups include, but are not limited to, heterosexual individuals (HET), men-who-have-sex-with-men (MSM), and people who inject drugs (PWID). Although genetically diverse HIV-1 populations transferred from donor to recipient, systemic infection is often established by a single clone, the transmitted/founder (T/F) virus. This phenomenon especially prevalent in sexual transmission, less stringent blood-to-blood contact transmission. Specific traits that permit successful transmission have been well characterized. Thus, containing chimeric T/F envelope (Env) different routes was assessed for ex vivo fitness performing mixed competition assays (also referred as competitions) on human cervical tissues. We found viruses isolated PWID exhibit replication capacity tissues when compared those MSM HET, diminishing their chances of T helper type (Th1) Th17 cells. reduced observed infecting Th1 cells directly, bypassing Phenotypic showed differed other having an enhanced ability utilize CCR5 conformations, while Env expression level, CD4/CCR5 utilization, entry speed did differ. Different glycosylation profiles were detected chronic with increased complex, fucosylated N- O-glycans more frequently Env. Furthermore, presence these glycans correlated In contrast, bisecting branched N-glycan associated decreased efficiency usage CCR5. These findings suggest patterns/levels and/or structure greatly impact differences HIV-1.