Full-Length HIV Type 1 Genome Analysis Showing Evidence for HIV Type 1 Transmission from a Nonprogressor to Two Recipients Who Progressed to AIDS

Abstract

Epidemiologically-linked HIV-1 transmission cohorts serve as excellent models to study HIV disease progression. The actual relationship between viral variability and HIV disease outcome can be extrapolated only through such rare epidemiologically linked HIV-1-infected cohorts. We present here a cohort of three patients with the source termed donor A (a nonprogressor) and two recipients B and C. Both recipients acquired HIV through blood transfusion from donor A and have progressed to AIDS. By analyzing 15 near full-length HIV- 1 genomes (8.7 kb each genome) from longitudinally collected peripheral blood cell samples (four time points for patient A, four for patient B, and seven from patient C), we were able to demonstrate transmission of HIV from donor A and epidemiologic linkage among members A, B, and C after 10 years of HIV infection. These analyses are novel in demonstrating that HIV-1-infected nonprogressing individuals bear the potential to transmit HIV-1 variants and that HIV variants, which led to a benign disease in a nonprogressor donor, were able to cause disease in other individuals. Overall, these studies highlight the utility of full genome sequencing in establishing epidemiologic linkage in a chronically infected HIV cohort after 10 years of initial infection.

The epidemic origin and molecular properties of B′: a founder strain of the HIV-1 transmission in Asia

“…However, even within these relatively poorly Although some sequences appeared to be more closely associated with the strongly clustered B 0 sequences, the relationship was not supported by high clade credibility, thus we were unable to clearly identify a sister cluster in the B subtype. It was also noted that a single B subtype sequence named 5127_86 [39] sampled in the United States in 1986 appeared to cluster comparatively stably with the B 0 group ( Fig. 1 and supplemental Fig.…”

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

“…This is the first large-scale analysis of influenza isolates collected in a relatively unbiased manner, allowing a comprehensive look at an influenza virus population across several seasons within a constrained geographical area. Among RNA viruses, only human immunodeficiency virus (HIV) has been subjected to similar wholegenome analysis 9,10 . In this first set of 209 genomes, we have observed multiple, novel mutational events, including point mutations, deletions and segment exchange.…”

Role of viral evolutionary rate in HIV-1 disease progression in a linked cohort

“…Successful amplification of near full-length HIV-1 genomes was achieved from a total of 15 PBMC patient samples collected between 1992 to 2000 from all 3 cohort members A, B and C. Epidemiological-linkage was confirmed by maximum likelihood phylogenetic analysis which was subsequently used for further intra patient evolutionary analysis as discussed previously in Mikhail et al ., 2005 [15]. …”

“…The rarity of such cohorts accents their existence as invaluable models for understanding how various host and viral factors govern HIV pathogenesis. For such purposes, we describe detailed molecular analyses of one such cohort comprising of 3 HIV-infected individuals (a non-progressing donor-A and two recipients B and C) whose epidemiological linkage was confirmed through phylogenetic analyses [15]. The donor A likely acquired HIV in 1982, and has remained healthy maintaining non-progressive status with high CD4 + and CD8 + T cell counts and with <7000 HIV-1 copies/ml of plasma.…”