2005/04/12 by Bangdong L. Wei, Paul W. Denton, Eduardo O’Neill +3 · 115 citations
Immunology and Microbiology · Medicine · #Biology #HIV Research and Treatment #Herpesvirus Infections and Treatments #Infectivity #Lentivirus #Lipid bilayer fusion #Mosquito-borne diseases and control #Vesicular stomatitis virus #Viral disease #Virology #Virus
paper · open access · doi:10.1128/jvi.79.9.5705-5712.2005
published in Journal of Virology 79(9), 5705-5712 (American Society for Microbiology)
openalex publication_date 2005/04/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
We previously reported that inhibition of endosomal/lysosomal function can dramatically enhance human immunodeficiency virus type 1 (HIV-1) infectivity, suggesting that under these conditions productive HIV-1 infection can occur via the endocytic pathway. Here we further examined this effect with bafilomycin A1 (BFLA-1) and show that this enhancement of infectivity extends to all HIV-1 isolates tested regardless of coreceptor usage. However, isolate-specific differences were observed in the magnitude of the effect. This was particularly evident in the case of the weakly infectious HIV-1(SF2), for which we observed the greatest enhancement. Using reciprocal chimeric viruses, we were able to determine that both the disproportionate increase in the infectivity of HIV-1(SF2) in response to BFLA-1 and its weak infectivity in the absence of BFLA-1 mapped to its envelope gene. Further, we found HIV-1(SF2) to have lower fusion activity and to be 12-fold more sensitive to the fusion inhibitor T-20 than HIV-1(NL4-3). Proteasomal inhibitors also enhance HIV-1 infectivity, and we report that the combination of a lysosomal and a proteasomal inhibitor greatly enhanced infectivity of all isolates tested. Again, HIV-1(SF2) was unique in exhibiting a synergistic 400-fold increase in infectivity. We also determined that inhibition of proteasomal function increased the infectivity of HIV-1 pseudotyped with vesicular stomatitis virus G protein. The evidence presented here highlights the important role of the lysosomes/proteasomes in the destruction of infectious HIV-1(SF2) and could have implications for the development of novel antiviral agents that might take advantage of these innate defenses.