Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro

Delassus, Sylvie; Cheynier, Rémi; Wain‐Hobson, Simon

doi:10.1128/jvi.65.1.225-231.1991

Cited by 135 publications

(58 citation statements)

References 35 publications

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“…It has been shown previously both in vitro and in vivo that the GA nucleotide substitution is the most frequent. [11][12][13][14][15][16][17][18] In contrast, studies on intrapatient sequence variation of the gag gene found no differences between proportions of GA and AG transitions. [19] A V106M mutation in RT is preferentially selected both in vitro and in vivo by the NNRTI efavirenz in subtype C viruses and confers high-level cross-resistance to all 3 currently approved NNRTIs.…”

Section: G190smentioning

confidence: 99%

Substitutions in the Reverse Transcriptase and Protease Genes of HIV‐1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs

Turner

Brenner

Moïsi

et al. 2005

Journal of the International AIDS Society

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The nucleotide transition G→A is known as a hypermutation due to its high prevalence in HIV-1 and other pathogens. However, the contribution of the G→A transition in the generation of drug resistance mutations is unknown. Our objective was to ascertain the rate of nucleotide substitutions in protease (PR) and reverse transcriptase (RT) in both untreated and treated HIV-1 patients. Genotypic analysis was performed on viruses from both treated and untreated patients with subtype B infections. Nucleotide genomic diversity was compared with a consensus subtype B reference virus. Then, the prevalence of resistance-associated mutations in different subgroups of treated patients was evaluated in relation to the patterns of nucleotide transitions. In untreated patients (n = 50) G→A was most prevalent, followed by A→G, C→T, and T→C transitions. In treated patients (n = 51), the prevalence of A→G was similar to that of G→A. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A→G transitions). Other frequent mutations in RT included T215Y (C→A and A→T substitutions), which was prevalent in 31% of treated patients. In PR, a L90M (T→A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. In conclusion, the G→A transition was most prevalent in RT and PR among untreated patients. In contrast, A→G was the most prevalent transition in patients treated with antiretroviral drugs.

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Section: G190smentioning

confidence: 99%

Substitutions in the Reverse Transcriptase and Protease Genes of HIV‐1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs

Turner

Brenner

Moïsi

et al. 2005

Journal of the International AIDS Society

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“…Significant genetic variation occurs within the human immunodeficiency virus (HIV) genome [reviewed by Leigh Brown, 19911. Many studies have shown that variation occurs in both a n inter-and intrapatient [Delassus et al, 1991[Delassus et al, , 1992Goodenow et al, 1989;Simmonds et al, 1990;Wain-Hobson, 19921 and that heterogeneity is not evenly distributed throughout the genome [Pedroza Martins et al, 1991, 19921. Thus, the hypervariable regions (Vl-V5) of the enu gene are significantly more heterogeneous than regions of the g a g gene [Leigh Brown and Monaghan, 1988;Balfe et al, 19901. The enu gene contains the principal neutralising determinant of HIV-1 [Rusche et al, 1988;Palker et al, 19881.…”

Section: Introductionmentioning

confidence: 99%

Sequence variation within the human immunodeficiency virus V3 loop at seroconversion

Ait‐Khaled

Emery

1993

Journal of Medical Virology

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Analysis of the HIV-1 V3 quasispecies present in an individual at the time of seroconversion was carried out. The polymerase chain reaction (PCR) was used to amplify proviral HIV-1 DNA extracted from peripheral blood mononuclear cells from a patient who was viraemic (p24 = 15 pg/ml) and had an equivocal HIV-1 antibody status. The PCR products were cloned and the DNA sequence determined for 15 clones. These data showed that the V3 region contained only limited sequence heterogeneity with a major variant accounting for 66% of the protein quasispecies present. The protein sequence of the principal neutralising domain on all species contained the relatively rare GPGKTL motif rather than GPGRAF. The relevance of these data for early stages of HIV infection are discussed.

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“…Although its mechanism of action is not understood, nefgene function has been shown to be essential for the maintenance of high levels of virus replication and the development of disease pathogenesis in the in vivo model of simian immunodeficiency virus (SIVmac) 1 infection of the macaque monkey (1). In HIV-1 infection of humans, there appears to be selective pressure for retention of highly conserved sequences of nefand an open reading flame (ORF) (2,3). In contrast to these data implying an important role for nefduring in vivo infection, the use of standard cell culture systems to study nef function in vitro has produced a wide spectrum of contradictory results.…”

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confidence: 99%

The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes.

Spina

Kwoh

Chowers

et al. 1994

The Journal of Experimental Medicine

380

281

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SummaryThe viral regulatory gene, nef, is unique to the human immunodeficiency viruses (HIV) and their related primate lentiviruses. Expression of the nefgene has been shown to be essential to the maintenance of high levels of virus replication and the development of pathogenesis in the animal model of simian immunodeficiency virus (SIV) infection. In contrast to this in vivo model, the use of standard T cell culture systems to study neffunction in vitro has produced a spectrum of contradictory results, and has failed to demonstrate a significant positive influence of nefon viral life cycle. We have developed a cell model to study regulation of HIV-1 replication that we believe reflects more accurately virus-cell interactions as they occur in vivo. Our experimental system used acute virus infection of purified, quiescent CD4 lymphocytes and subsequent induction of viral replication through T cell activation. With this cell model, NL4-3 virus clones with open and mutated nef reading frames were compared for replication competence. The clones with nefmutations showed reproducible and significant reductions in both rates of growth and maximal titers achieved. The degree of reduced replication was dependent on initial virus inoculum and the timing of T cell activation. The influence of nef was highly significant for induction of virus replication from a latent state within resting CD4 cells. Its effect was less apparent for virus infection of fully proliferating CD4 cells. This study demonstrates that nefconfers a positive growth advantage to HIV-1 that becomes readily discernable in the primary cell setting of virus induction through T cell activation. The experimental cell model, which we describe here, provides not only a means to study neffunction in vitro, but also provides important clues to the function of nef in HIV infection in vivo.

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Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro

Cited by 135 publications

References 35 publications

Substitutions in the Reverse Transcriptase and Protease Genes of HIV‐1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs

Substitutions in the Reverse Transcriptase and Protease Genes of HIV‐1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs

Sequence variation within the human immunodeficiency virus V3 loop at seroconversion

The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes.

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