Inhibition of Lysosome and Proteasome Function Enhances Human Immunodeficiency Virus Type 1 Infection

• DOI: 10.1128/jvi.79.9.5705-5712.2005
• Publication Date: 2005-04-12T17:13:56Z
• Authors: Bangdong L. Wei; Paul W. Denton; Eduardo O'Neill; Tianci Luo; John L. Foster; J. Victor Garcia
• Keywords: Infectivity

We previously reported that inhibition of endosomal/lysosomal function can dramatically enhance human immunodeficiency virus type 1 (HIV-1) infectivity, suggesting under these conditions productive HIV-1 infection occur via the endocytic pathway. Here we further examined this effect with bafilomycin A1 (BFLA-1) and show enhancement infectivity extends to all isolates tested regardless coreceptor usage. However, isolate-specific differences were observed in magnitude effect. This was particularly evident case weakly infectious HIV-1(SF2), for which greatest enhancement. Using reciprocal chimeric viruses, able determine both disproportionate increase HIV-1(SF2) response BFLA-1 its weak absence mapped envelope gene. Further, found have lower fusion activity be 12-fold more sensitive inhibitor T-20 than HIV-1(NL4-3). Proteasomal inhibitors also report combination a lysosomal proteasomal greatly enhanced tested. Again, unique exhibiting synergistic 400-fold infectivity. determined increased pseudotyped vesicular stomatitis G protein. The evidence presented here highlights important role lysosomes/proteasomes destruction could implications development novel antiviral agents might take advantage innate defenses.