Background: Semen enhances HIV infection in vitro, and semen-derived amyloids made up of a peptide from the abundant protein semenogelin 1 (SEM1) are sufficient to mediate this activity. We sought to compare the infectivity-enhancing activity of semen among HIV infected men, and examine its relationship to concentrations of amyloidogenic peptides.
Methods: We studied 188 paired seminal and blood plasma samples from 113 individual UCSF Options study subjects at least four months after acute HIV infection. 20 subjects were studied at multiple timepoints prior to ART; 20 were studied before and after suppressive ART and 20 before and after ART interruption. Quantitative mass spectrometry and ELISAs were used to quantify amyloidogenic SEM peptide fragments. Semen-mediated enhancement of HIV infection was measured by mixing serial dilutions of each sample with HIV prior to adding it to TZM-bl reporter cells, and assessing infection levels by luminescence 3 days later. Seminal fluid VL was quantified using Abbott RealTime PCR.
Results: Semen from HIV infected men enhanced HIV infectivity (mean 10.8-fold, range from 0- to >35-fold enhancement). Levels of endogenous amyloidogenic SEM were correlated with the infectivity-enhancing activity of semen samples (r=0.48;p<.0001). For individual subjects with longitudinal samples, levels of both infectivity enhancement and SEM tended to be similar over time (intraclass correlations (ICCs) for infectivity enhancement 0.33, SEM 0.49, semen VL 0.42). Infectivity enhancing activity of semen had little association with ART naïve semen VL (r=-0.08). With interruption of ART (baseline semen VL<200 cp/mL in 18/20 subjects), there was no systematic increase in either infectivity enhancement (mean 18% decrease, p=0.17) or SEM (mean 13% decrease, p=0.054).
Conclusions: Our results suggest that semen from HIV infected men can enhance the efficiency with which HIV infects permissive cells, in a manner that persists in men taking ART and is independent of semen VL but is directly associated with levels of amyloidogenic SEM fragments. The HIV-enhancing activities of multiple semen samples from the same individual were relatively similar, even upon ART treatment, suggesting that the HIV enhancing activity of semen can be considered an individual characteristic. Together, these data suggest that individual semen characteristics other than HIV VL may be important factors in HIV transmission.