Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source

<p>Abstract</p> <p>Background</p> <p>The Sydney blood bank cohort (SBBC) of long-term survivors consists of multiple individuals infected with attenuated, <it>nef</it>-deleted variants of human immunodeficiency virus type 1 (HIV-1) acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP) as well as long-term nonprogressors (LTNP). Convergent evolution of <it>nef </it>sequences in SBBC SP and LTNP indicates the <it>in vivo </it>pathogenicity of HIV-1 in SBBC members is dictated by factors other than <it>nef</it>. To better understand mechanisms underlying the pathogenicity of <it>nef</it>-deleted HIV-1, we examined the phenotype and <it>env </it>sequence diversity of sequentially isolated viruses (n = 2) from 3 SBBC members.</p> <p>Results</p> <p>The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-1 infection (subjects D36 and C98, respectively) and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection (subject C18). Both isolates from D36 were R5X4 phenotype and, compared to control HIV-1 strains, replicated to low levels in peripheral blood mononuclear cells (PBMC). In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of <it>env </it>by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter-patient <it>env </it>evolution.</p> <p>Conclusion</p> <p>Independent evolution of <it>env </it>despite convergent evolution of <it>nef </it>may contribute to the <it>in vivo </it>pathogenicity of <it>nef</it>-deleted HIV-1 in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity.</p

Phenotype and envelope gene diversity of -deleted HIV-1 isolated from long-term survivors infected from a single source-4

<p><b>Copyright information:</b></p><p>Taken from "Phenotype and envelope gene diversity of -deleted HIV-1 isolated from long-term survivors infected from a single source"</p><p>http://www.virologyj.com/content/4/1/75</p><p>Virology Journal 2007;4():75-75.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC1939844.</p><p></p>-1 infected PBMC and subjected to GeneScan analysis, as described in the Methods and elsewhere [41, 56]. (A) GeneScan sample files generated from amplified products. (B) Fraction of sequences with a given V1V2 nucleotide length, which was calculated from GeneScan sample files. Peaks and bars shown in red represent V1V2 amplimers from early viruses, and peaks and bars shown in blue represent V1V2 amplimers from late viruses. Similar results were obtained in two independent experiments

Phenotype and envelope gene diversity of -deleted HIV-1 isolated from long-term survivors infected from a single source-0

<p><b>Copyright information:</b></p><p>Taken from "Phenotype and envelope gene diversity of -deleted HIV-1 isolated from long-term survivors infected from a single source"</p><p>http://www.virologyj.com/content/4/1/75</p><p>Virology Journal 2007;4():75-75.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC1939844.</p><p></p>roduction in culture supernatants was measured by RT assays. Values shown are means from duplicate infections. Error bars represent standard deviations. Results are representative of two independent experiments using cells obtained from different donors