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Correlation between env V1/V2 Region Diversification and Neutralizing Antibodies during Primary Infection by Simian Immunodeficiency Virus sm in Rhesus Macaques

Correlation between env V1/V2 Region Diversification and Neutralizing Antibodies during Primary Infection by Simian Immunodeficiency Virus sm in Rhesu

Correlation between env V1/V2 Region Diversification and Neutralizing Antibodies during Primary Infection by Simian Immunodeficiency Virus sm in Rhesus Macaques   (Citations: 17)
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Evolution of the domain encoding the V1/V2 variable region of the simian immunodeficiency virus sm (SIVsm) envelope (env) gene was analyzed in relation to route of virus challenge, virus load, and neutralizing antibody (NAb) titers during primary infection of rhesus macaques with the pathogenic SIVsmE660 isolate. In this model system animals are initially infected with multiple viruses as evidenced by the presence of multiple V1/V2 genotypic variants that could be resolved by using a heteroduplex tracking assay (HTA). Overlapping subsets of the multiple variants were established in each animal. There was no selection for the establishment of specific variants in comparing intravenous- and intrarectal-challenged macaques at week 2 postinfection, suggesting that no genotypic selection occurred at the mucosal surface. There was an initial period of significant stability of the V1/V2 variants. Macaques challenged intravenously displayed subsequent V1/V2 diversification significantly earlier than macaques challenged intrarectally and well past the initial resolution of viremia. The time when SIVsmE660-specific NAbs reached a threshold titer of 100 was significantly correlated with the timing of V1/V2 diversification, even though antibodies to the Env protein could be detected much earlier. The time when NAbs reached a titer of 400 was significantly correlated with virus load late in infection. These results show that the route of infection affects the timing of V1/V2 diversification and that this diversification is correlated with the maturation of a specific NAb response. However, prior immunization capable of priming an anamnestic Env antibody response did not accelerate V1/V2 diversification. This result suggests that diversification of the SIV env V1/V2 region is the result of a type-specific antibody response.
Journal: Journal of Virology - J VIROL , vol. 78, no. 7, pp. 3561-3571, 2004
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    • ...Despite these limitations, the analyses presented here and the work of others ...

    Marcel E. Curlinet al. HIV1 Envelope Subregion Length Variation during Disease Progression

    • ...Genetic evolution during SIV infection has been well documented in comparison with the evolution of HIV-1 population [15-18]...

    Benjamin N Bimberet al. Nef gene evolution from a single transmitted strain in acute SIV infec...

    • ...The early changes observed in the C2, V1, V2, and V3 regions appeared concomitantly with the emergence of homologous neutralizing antibody responses (Table 1), and therefore it is possible that the initial neutralizing antibody response to SHIVSF162P4-infection targets these four envelope regions, as has been previously reported in the case of SIVsm-infected macaques (38)...

    Zane Kraftet al. Macaques Infected with a CCR5Tropic Simian/Human Immunodeficiency Viru...

    • ...The wide variation in these variable regions, as well as high conservation of other regions, suggested that these substitutions might be selected to escape from immune recognition, as previously reported (3, 6, 7, 26, 28, 36, 51, 55, 56)...
    • ...This is consistent with the hypothesis that these mutations in variable regions are due to escape from antibody recognition (3, 6, 7, 26, 28, 36, 51, 55, 56)...
    • ...Compared with this rapid reversion, changes in the V1-V2 and V4 regions of Env that are commonly observed in a conventional escape from neutralizing antibodies (3, 6, 7, 26, 28, 36, 51, 55, 56) occurred by later time points...
    • ...The observation of positive selection of amino acid changes, insertion/deletion polymorphisms, and changes of PNG sites in the V1-V2 and V4 regions are characteristic of escape from neutralizing antibodies (3, 6, 7, 26, 28, 36, 51, 55, 56)...

    Takeo Kuwataet al. A Rapid Progressor-Specific Variant Clone of Simian Immunodeficiency V...

    • ...Our results were in line with the observations of Rybarczyk et al. (2004), who found that neutralizing antibodies against the challenge virus SIVsmE660 could be detected at 7 weeks after infection in IV-challenged macaques, whereas at this time the IRchallenged macaques did not have detectable neutralizing antibodies (Rybarczyk et al., 2004)...
    • ...Our results were in line with the observations of Rybarczyk et al. (2004), who found that neutralizing antibodies against the challenge virus SIVsmE660 could be detected at 7 weeks after infection in IV-challenged macaques, whereas at this time the IRchallenged macaques did not have detectable neutralizing antibodies (Rybarczyk et al., 2004)...
    • ...Rybarczyk et al. (2004) showed that the timing of detectable neutralizing antibodies in macaques correlated with the timing of V1/V2 diversification, used by the authors as a marker for measuring the complexity of viral populations...
    • ...In the system explored by Rybarczyk et al. (2004), macaques challenged by the IV route displayed subsequent V1/V2 diversification from homogeneous V1/V2 variants significantly earlier than macaques challenged by the IR route...

    Anna Laurenet al. Comparative studies on mucosal and intravenous transmission of simian ...

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