A highly defective HIV-1 strain isolated from a healthy Gabonese individual presenting an atypical Western blot

Huet, Thierry; Dazza, Marie-Christine; Brun‐Vézinet, Françoise; Roelants, Georges E.; Wain‐Hobson, Simon

doi:10.1097/00002030-198911000-00004

Cited by 63 publications

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“…Apart from human genetic factors, the result of this study suggests that the primary and tertiary structures of Tat variants can dramatically influence the magnitude and breadth of antibody response against Tat. The choice of Tat Oyi to represent Tat variants from long term non-progressor patients was motivated by a follow up of HIV infection during the eighties in a remote area of Gabon showing that a large majority of HIV-infected patients were long term non-progressors (26). The high proportion of long term non-progressors was difficult to explain by genetic factors, and our hypothesis is that these individuals developed an immune response against Tat.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis was not mentioned by Huet et al (26) because the role of extracellular Tat was unknown at that time. However, the authors mentioned that the tat gene was defective because of the mutation C22S, and reversion of this mutation could lead to an effective tat gene (26).…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that this immune property induced a long term nonprogressor phenotype for individuals infected with the HIV-1 Oyi strain. HIV-1 Oyi had a low virulence because the tat gene was defective, but patients infected with HIV-1 Oyi were protected against highly virulent D-subtypes (26). Although the HIV-1 Oyi strain was classified as a B-subtype, Tat Oyi has sequence homology with other subtypes of Tat that are not found in a regular B-subtype of Tat, such as HXB2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, clinical studies show that an immune response against Tat correlates with the low viral load in HIV-1 seropositive patients in the absence of antiretroviral therapy (3,24,25). Interestingly, an epidemiological study in Gabon showed that patients infected by the HIV-1 Oyi strain were long term non-progressors (26). No anomaly was found in the virus sequence except in the gene tat where the mutation of cysteine 22 to serine seemed to account for the loss of transactivation activity (26).…”

mentioning

confidence: 99%

“…Interestingly, an epidemiological study in Gabon showed that patients infected by the HIV-1 Oyi strain were long term non-progressors (26). No anomaly was found in the virus sequence except in the gene tat where the mutation of cysteine 22 to serine seemed to account for the loss of transactivation activity (26). * This work was supported by the Agence National pour la Recherche contre le SIDA (ANRS), Agence Nationale pour la Valorisation de la Recherche (ANVAR), and the Centre National pour la Recherche Scientifique (CNRS).…”

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confidence: 99%

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Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants

Opi¹,

Péloponèse²,

Esquieu³

et al. 2002

Journal of Biological Chemistry

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Clinical studies show that in the absence of anti-retroviral therapy an immune response against the human immunodeficiency virus type 1 (HIV-1), transacting transcriptional activator (Tat) protein correlates with long term non-progression. The purpose of this study is to try to understand what can trigger an effective immune response against Tat. We used five Tat variants from HIV strains identified in different parts of the world and showed that mutations of as much as 38% exist without any change in activity. Rabbit sera were raised against Tat variants identified in rapid-progressor patients (Tat HXB2, a European variant and Tat Eli, an African variant) and a long term non-progressor patient (Tat Oyi, an inactive African variant). Enzymelinked immunosorbent assay (ELISA) results showed that anti-Tat Oyi serum had the highest antibody titer and was the only one to have a broad antibody response against heterologous Tat variants. Surprisingly, Tat HXB2 was better recognized by anti-Tat Oyi serum compared with anti-Tat HXB2 serum. Western blots showed that non-homologous Tat variants were recognized by antibodies directed against conformational epitopes. This study suggests that the primary and tertiary structures of the Tat variant from the long term non-progressor patient are critical to the induction of a broad and effective antibody response against Tat.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants

Opi¹,

Péloponèse²,

Esquieu³

et al. 2002

Journal of Biological Chemistry

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In vivo persistence of a HIV‐1‐encoded HLA‐B27‐restricted cytotoxic T lymphocyte epitope despite specific in vitro reactivity

et al. 1991

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A large number of human immunodeficiency virus type 1 (HIV-1) specific HLA-restricted cytotoxic T cell (CTL) epitopes have been mapped, including an HLA-B27-restricted immunodominant epitope within p25gag. Accordingly, this segment of the HIV-1 provirus was amplified by the polymerase chain reaction from DNA derived from fresh uncultured peripheral blood mononuclear cells (PBMC) of four HLA-B27 HIV-1-infected individuals. In all cases the majority of infected PBMC bore sequences encoding the HLA-B27-restricted peptide. CTL escape mutants had not accumulated in vivo 8 and 14 months later despite demonstrable CTL activity in vitro. These data emphasize the importance of silently infected lymphocytes in evading immune surveillance.

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Evolution of the primate lentiviruses: evidence from vpx and vpr.

et al. 1992

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The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV‐2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV‐2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV‐2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.

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A highly defective HIV-1 strain isolated from a healthy Gabonese individual presenting an atypical Western blot

Cited by 63 publications

References 0 publications

Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants

Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants

In vivo persistence of a HIV‐1‐encoded HLA‐B27‐restricted cytotoxic T lymphocyte epitope despite specific in vitro reactivity

Evolution of the primate lentiviruses: evidence from vpx and vpr.

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