Genetic variability of the V1 and V2 env domains of SIVcpz‐ant and neutralization pattern of plasma viruses in a chimpanzee infected naturally

Abstract

Specific neutralizing epitope changes have been observed in a chimpanzee infected naturally with SIVcpz, which differ from HIV-1 infecting humans. To characterize further these changes, a longitudinal study of env genomic sequence variation of SIVcpz-ant isolates was undertaken in this animal. The V1 and V2 regions of the env were determined to arise from specific recombination events. To determine whether recombination of the V1 and V2 domains was possibly associated with the emergence of neutralization escape viruses, envelope sequences and gene length polymorphisms from PBMC and plasma viral variants were studied over a 7-year period. PBMCs and plasma-associated infectious virus titers as well as plasma RNA viral loads were monitored longitudinally. The first 5 viruses isolated from the plasma were found to be neutralization escape variants. Sequence analysis of their V1 and the V2 regions indicated that a 20 amino acid stretch of the V1 region had undergone recombination and was also associated with the emergence of isolates eliciting strong neutralization responses. These findings support the hypothesis that recombination of the V1 and V2 regions of the envelope play a role in neutralization escape of SIVcpz in chimpanzees infected naturally. Furthermore, the data confirm that the neutralizing antibody response plays an important role in the decline of plasma infectious virus titers in HIV-1 related SIVcpz nonpathogenic infection.

Noninvasive Follow-Up of Simian Immunodeficiency Virus Infection in Wild-Living Nonhabituated Western Lowland Gorillas in Cameroon

“…Furthermore, we observed a significantly increased number of PNGS in the V1V2 region over time. Like that of SIVcpz in naturally infected chimpanzees (13,37) or SIVsmm in naturally infected sooty mangabeys (10), SIVgor V1V2 appears to be highly glycosylated. An increasing number of PNGS in the gp120 hypervariable loops of HIV-1 has been associated with the escape of viral mutants (31,59).…”

Inter‐subtype cross‐neutralizing antibodies recognize epitopes on cell‐associated HIV‐1 virions

“…With other lentiviruses, antibodies that are highly specific for individual variants have been reported [Rwambo et al, 1990;Stipp et al, 2000]. Their specificity becomes broader in response to escape variants as these emerge until the antibodies can neutralize the wide range of variants within their own host [Hammond et al, 2000;Ondoa et al, 2001]. The situation appears to be similar for HIV: although HIV can be classified into subtypes by comparing the nucleotide sequences of their envelope genes, there is no equivalent division into neutralization serotypes, with the exception of subtypes B and E [Mascola et al, 1994].…”

“…It may be that primary isolates can resist the effect of these antibodies' binding and still replicate, albeit at a reduced rate. Cross-neutralization of primary isolates has been associated with long term survival in HIV infected subjects Montefiori et al, 1996;Pilgrim et al, 1997;Zhang et al, 1997;Carotenuto et al, 1998], but if these antibodies are merely influencing the replication rate of the virus (either reducing ¼ neutralization, or increasing ¼ enhancing [Montefiori et al, 1996;Davis et al, 2001]), coupled with the capacity of lentiviruses to recombine [Ondoa et al, 2001], these people are dwelling in the realm of the Red Queen [Domingo et al, 1996] and there is no immediately obvious opportunity to emigrate.…”

Single Real-Time Reverse Transcription-PCR Assay for Detection and Quantification of Genetically Diverse HIV-1, SIVcpz, and SIVgor Strains

“…Previously, Kestens et al observed a fluctuating pattern with the measurement of virus titers in plasma varying from undetected to 1,000 tissue culture infectious doses/ml (49). From the end of 1997 to 2001 (i.e., dates after our panel), Ondoa et al quantified viral RNA from Ch-No plasma samples with a specific in-house assay, and the values varied from 3.93 to 5.80 log 10 copies/ml (50,51), in the range of our viral loads. Therefore, despite the high genetic distances between SIVcpz strains, our assay was able to detect and quantify the SIVcpzPtt and SIVcpzPts RNA from chimpanzee plasma samples.…”