Inhibitory Effects of HIV-2 Vpx on Replication of HIV-1.

Human immunodeficiency virus type 1 (HIV-1) and HIV-2 share a striking genomic resemblance; however, variability in the genetic sequence accounts for the presence of unique accessory genes, such as the viral protein X (vpx) gene in HIV-2. Dual infection with both viruses has long been described in the literature, yet the molecular mechanism of how dually infected patients tend to do better than those who are monoinfected with HIV-1 has not yet been explored. We hypothesized that in addition to extracellular mechanisms, an HIV-2 accessory gene is the culprit, and interference at the viral accessory/regulatory protein level is perhaps responsible for the attenuated pathogenicity of HIV-1 observed in dually infected patients. Following simulation of dual infection in cell culture experiments, we found that pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction. Importantly, we have found that this dampening of the infectivity of HIV-1 was a result of interviral interference carried out by viral protein X of HIV-2, resulting in a severe hindrance to the replication dynamics of HIV-1, influencing both its early and late phases of the viral life cycle. Our findings shed light on potential intracellular interactions between the two viruses and broaden our understanding of the observed clinical spectrum in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV-1.IMPORTANCE Dual infection with human immunodeficiency virus types 1 and 2 is relatively common in areas of endemicity. For as-yet-unclarified reasons, patients who are dually infected were shown to have lower viral loads and generally a lower rate of progression to AIDS than those who are monoinfected. We aimed to explore dual infection in cell culture, to elucidate possible mechanisms by which HIV-2 may be able to exert such an effect. Our results indicate that on the cellular level, pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction, which was found to be a result of interviral interference carried out by viral protein X of HIV-2. These findings broaden our knowledge of interviral interactions on the cellular level and may provide an explanation for the decreased pathogenicity of HIV-1 in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV.