Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity.
We have investigated the effects of Nef on infectivity in the context of various viral envelope proteins. These experiments were performed with a minimal vector system where Nef is the only accessory protein present. Our results support the hypothesis that the route of entry influences the ability of Nef to enhance human immunodeficiency virus (HIV) infectivity. We show that HIV particles pseudotyped with Ebola virus glycoprotein or vesicular stomatitis virus glycoprotein (VSV-G), which fuse at low pH, do not require Nef for optimal infectivity. In contrast, Nef significantly enhances the infectivity of virus particles that contain envelope proteins that fuse at neutral pH (CCR5-dependent HIV Env, CXCR4-dependent HIV Env, or amphotropic murine leukemia virus Env). In addition, our results demonstrate that virus particles containing mixed CXCR4-dependent HIV and VSV-G envelope proteins show a conditional requirement for Nef for optimal infectivity, depending on which protein is allowed to facilitate entry.
Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, Virginia 22908, USA.
N
N
Chazal
G
G
Singer
C
C
Aiken
M L
ML
Hammarskjöld
D
D
Rekosh
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D017353:Gene Deletion; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007106:Immune Sera / Q000276:immunology; D018942:Macrolides; D008561:Membrane Fusion; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus
D000900:Anti-Bacterial Agents; D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D015693:Gene Products, nef; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D018942:Macrolides; D008562:Membrane Glycoproteins; D015728:Receptors, HIV; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C040929:bafilomycin A1