Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions.
Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767(stop), which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752(N750K)) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752(N750K) exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses.
Devitt
Gerard
G
Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Emerson
Vanessa
V
Holtkotte
Denise
D
Pfeiffer
Tanya
T
Pisch
Thorsten
T
Bosch
Valerie
V
D002460:Cell Line; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006678:HIV / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009154:Mutation; D016865:Reassortant Viruses / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D038301:Virus Inactivation
D006023:Glycoproteins; D014759:Viral Envelope Proteins