2-AIN-506 a 2-AIN-252: Seminár z bioinformatiky (2) a (4)
Leto 2017

Michael Worobey, Thomas D. Watts, Richard A. McKay, Marc A. Suchard, Timothy Granade, Dirk E. Teuwen, Beryl A. Koblin, Walid Heneine, Philippe Lemey, Harold W. Jaffe. 1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in NorthAmerica. Nature, 539(7627):98-101. 2016.

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The emergence of HIV-1 group M subtype B in North American men who have sex with 
men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have
suggested cryptic subtype B circulation in the United States (US) throughout the 
1970s and an even older presence in the Caribbean. However, these temporal and
geographical inferences, based upon partial HIV-1 genomes that postdate the
recognition of AIDS in 1981, remain contentious and the earliest movements of the
virus within the US are unknown. We serologically screened >2,000 1970s serum
samples and developed a highly sensitive approach for recovering viral RNA from
degraded archival samples. Here, we report eight coding-complete genomes from US 
serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to
date. This early, full-genome 'snapshot' reveals that the US HIV-1 epidemic
exhibited extensive genetic diversity in the 1970s but also provides strong
evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian
phylogenetic analyses estimate the jump to the US at around 1970 and place the
ancestral US virus in New York City with 0.99 posterior probability support,
strongly suggesting this was the crucial hub of early US HIV/AIDS
diversification. Logistic growth coalescent models reveal epidemic doubling times
of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid
early expansion in each location. Comparisons with more recent data reveal many
of these insights to be unattainable without archival, full-genome sequences. We 
also recovered the HIV-1 genome from the individual known as 'Patient 0' (ref. 5)
and found neither biological nor historical evidence that he was the primary case
in the US or for subtype B as a whole. We discuss the genesis and persistence of 
this belief in the light of these evolutionary insights.