The Vif protein of human immunodeficiency virus type 1 (HIV-1) is essential for the infectivity of virions produced by non-permissive cells. The primary replicative defect of Vif particles involves either synthesis or stability of viral DNA, but the mechanism of this defect is unknown. Here, we report the results of a detailed analysis of HIV-1 DNA synthesis by isogenic VifNmutants produced by different chronically infected H9 clones, which exhibit different degrees of impairment in their replicative capacity. We found that the degree of impairment of DNA synthesis by the mutant particles always correlated with the degree of their loss of infectivity. This impairment appears to be global, with a defect increasing along with synthesis of longer viral DNA species. We conclude that the primary replicative defect of Vif virus involves the capacity of the reverse transcription complex of HIV-1 to efficiently elongate viral DNA, resulting in an inability to produce full-length viral DNA genomes.
BormanA. M.,
QuillentC.,
CharneauP.,
DauguetC.,
ClavelF.1995; Human immunodeficiency virus type 1 Vif− mutant particles from restrictive cells : role of Vif in correct particle assembly and infectivity. Journal of Virology 69:2058–2067
BouyacM.,
ReyF.,
NascimbeniM.,
CourcoulM.,
SireJ.,
BlancD.,
ClavelF.,
VigneR.,
SpireB.1997; Phenotypically Vif− human immunodeficiency virus type 1 is produced by chronically infected restrictive cells. Journal of Virology 71:2473–2477
CourcoulM.,
PatienceC.,
ReyF.,
BlancD.,
HarmacheA.,
SireJ.,
VigneR.,
SpireB.1995; Peripheral blood mononuclear cells produce normal amounts of defective Vif− human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps. Journal of Virology 69:2068–2074
GabuzdaD.,
LawrenceK.,
LanghoffE.,
TerwilligerE.,
DorfmanT.,
HaseltineW.,
SodroskiJ.1992; Role of Vif in replication of HIV type 1 in CD4+ T lymphocytes. Journal of Virology 66:6489–6495
GonsalvesJ.,
JallepalliP.,
GabuzdaD.1994; Subcellular localization of the Vif protein of human immunodeficiency virus type-1. Journal of Virology 68:704–712
GonçalvesJ.,
KorinY.,
ZackJ.,
GabuzdaD.1996; Role of Vif in human immunodeficiency virus type 1 reverse transcription. Journal of Virology 70:8701–8709
GuyaderM.,
EmermanM.,
SonigoP.,
ClavelF.,
MontagnierL.,
AlizonM.1987; Genetic organization and transactivation of human immunodeficiency virus type 2. Nature 326:662–669
KarczewskiM.,
StrebelK.1996; Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein. Journal of Virology 70:494–507
LiuH.,
WuX.,
NewmanM.,
ShawG. M.,
HahnB. H.,
KappesJ. C.1995; The Vif protein of human and simian immunodeficiency viruses is packaged into virions and associates with viral core structures. Journal of Virology 69:7630–7638
SakaiH.,
ShibataR.,
SakuragiJ.-I.,
SakuragiS.,
KawamuraM.,
AdachiA.1993; Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles. Journal of Virology 67:1663–1666
SimonJ. H. M.,
MalimM. H.1996; The human immunodeficiency virus type 1 Vif protein modulates the postpenetration stability of viral nucleoprotein complexes. Journal of Virology 70:5297–5305
SonigoP.,
AlizonM.,
StaskusK.,
KlatzmannD.,
ColeS.,
DanosO.,
RetzelE.,
TiollaisP.,
HaaseA.,
Wain-HobsonS.1985; Nucleotide sequence of the Visna lentivirus: relationship to the AIDS virus. Cell 43:369–382
SovaP.,
VolskyD.1993; Efficiency of viral DNA synthesis during infection of permissive and non-permissive cells with Vif−negative HIV-1. Journal of Virology 67:6322–6326
Von SchwedlerU.,
SongJ.,
AikenC.,
TronoD.1993; Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. Journal of Virology 67:4945–4955