Shapiro S, Hsu M, Harouse J, Cheng-Mayer C, Balfe P; Conference on Retroviruses and Opportunistic Infections.
9th Conf Retrovir Oppor Infect Feb 24 28 2002 Wash State Conv Trade Cent Seattle Wash Conf Retrovir Oppor Infect 9th 2002 Seattle Wash. 2002 Feb 24-28; 9: abstract no. 358-M.
Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY
BACKGROUND: Serial blood-bone marrow transfer of the R5-tropic SHIV(SF162) in 4 pairs of naive macaques was performed during their seronegative window period (2 weeks post exposure). Increased replication of the virus was observed with each successive in vivo passage, with one animal in the passage 3 group (T353) rapidly progressing to an AIDS defining illness at 20 weeks. PMBC were collected from all animals at weekly intervals during acute infection. We characterized HIV-1 envelope sequences in the serially passaged animals with the goal of identifying changes in gp120 that could account for adaptation and increased pathogenicity of the virus in vivo.METHODS: PCR and sequencing of the gp120 region was performed on samples obtained shortly before (1 week) and shortly after (3 weeks) the time of viral transfer in each animal. Samples from T353 at subsequent time points post exposure were also analysed.RESULTS: 5 replicate sequences of near complete gp120 regions (1450 bp) were obtained from each sample and phylogenetic analyses performed to assess the relationship between the sequences derived from the earlier and later samples. This large amount of sequence data allowed for highly robust analysis. Bootstrap re-sampling and maximum likelihood analyses of the data set failed to identify any cladistic information across the 8 animals investigated, indicating that no structure existed which discriminated early passage from later passage sequences. However, measurement of the intra-sample variability in the later passage material indicated that the '"quasi-species'" diversity in the later transfers had increased. Conclusion: Despite evidence of enhanced replicative growth and pathogenicity in vivo, sequencing of the virus present in the passaged animals at 1 and 3 weeks post exposure suggested that the original tissue culture virus SHIV(SF162) did not show any change in gp120 consensus sequence prior to seroconversion. The only changes seen were a significant increase in the pair-wise distances between the sequences obtained. These surprising observations lead us to conclude firstly that prior to seroconversion, the expansion of the virus in vivo does not lead to the emergence of a new macaque- specific gp120 sequence and secondly that the observed increase in pathogenicity on serial passage may be due more to the increase in viral diversity (and hence in the ability to escape immune selection) than to any directional adaptive change in the gp120 gene.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Animals
- Base Sequence
- Evolution
- HIV
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seronegativity
- HIV Seropositivity
- HIV-1
- Macaca
- Macaca mulatta
- Macaca nemestrina
- Serial Passage
- Simian Acquired Immunodeficiency Syndrome
- Sjogren's Syndrome
- genetics
- immunology
Other ID:
UI: 102263528
From Meeting Abstracts