Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

Abstract

HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type-specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses.

Heterogeneity in Neutralization Sensitivities of Viruses Comprising the Simian Immunodeficiency Virus SIVsmE660 Isolate and Vaccine Challenge Stock

“…It is interesting, though not entirely unexpected given their common origin and degree of genetic homology (9,13,14,16), to note the extent to which the SIVsmE660 and HIV-2 neutralization profiles overlap. Three recent studies of the antibody response to HIV-2 infection independently demonstrated that HIV-2-infected individuals mount high-titer, broadly reactive NAb responses (39,95,96). Similar to the uncloned SIVsmE660 isolate and Envs described here, the majority of primary HIV-2 strains, including SGA-derived Envs, were highly sensitive to antibody-mediated neutralization through multiple exposed epitopes (V3, CD4i, CD4bs, and V4), suggesting that SIVsmE660 and HIV-2 have more open, flexible Env conformations, akin to those of lab-adapted HIV-1 strains and distinct from those of primary HIV-1 isolates and T/F viruses (39).…”

“…We also demonstrated that the uncloned isolate possesses a minor fraction of substantially more resistant viruses, and this dichotomy could have unanticipated effects on the outcome of low-dose SIVsmE660 challenge studies in terms of both disease natural history and vaccine-elicited immune protection by Env antibodies. While these features of the SIVsmE660-rhesus infection model distinguish it from HIV-1 infection in humans, they have interesting and still-unexplained parallels with HIV-2 infection of humans (39,95,96). The converse of these features of SIVsmE660 and HIV-2 neutralization sensitivity is the property of pan-neutralization resistance of SIVmac251 and SIVmac239, which mechanistically remains largely unexplained (17)(18)(19)100).…”

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

“…For the analyses of the neutralizing activity of HIV-positive plasma, two HIV isolates, one HIV-1 and one HIV-2, were used. The HIV-1 circulating recombinant form (CRF)02_AG isolate, AG GB/30, originated from the same Guinea-Bissau study population from which the analyzed plasma was obtained (9,30). The HIV-2 subtype A isolate, A WA/P1-1991, originated from West Africa (10) and was isolated by cocul- (10) with reagents from Jackson Immunotech (Marseille, France).…”

“…In addition, neutralization escape mutants emerge less frequently, if at all, in HIV-2 infection; this suggests that the HIV-2 envelope glycoprotein complex (Env) might play an important role in eliciting a more effective immune response (7)(8)(9)(10). Indeed, the HIV-2 Env has been found to display multiple broadly cross-reactive epitopes and CD4 independence, both of which are characteristics that are uncommon in the HIV-1 Env (11).…”

“…In this study, we compared, side-by-side, the breadth and potency of intra-and intertype NAc in plasma against a panel of HIV-1 and HIV-2 isolates and found that the potency of intratype NAc in HIV-2 infection was significantly higher than in HIV-1 infection (9). Interestingly, plasma from dually HIV-1-and HIV-2 (HIV-D)-infected individuals, tested for the first time, was found to display potent NAc against HIV-2 but not HIV-1, suggesting differences in the immunogenicity and/or antigenicity of the two viruses.…”