Journal
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
Volume 279, Issue 1741, Pages 3367-3375Publisher
ROYAL SOC
DOI: 10.1098/rspb.2012.0595
Keywords
HIV; mathematical model; rate of evolution; viral latency
Categories
Funding
- Wellcome Trust
- Royal Society
- Medical Research Council
- Medical Research Council [G0800596, G0600719B] Funding Source: researchfish
- MRC [G0800596] Funding Source: UKRI
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Over calendar time, HIV-1 evolves considerably faster within individuals than it does at the epidemic level. This is a surprising observation since, from basic population genetic theory, we would expect the genetic substitution rate to be similar across different levels of biological organization. Three different mechanisms could potentially cause the observed mismatch in phylogenetic rates of divergence: temporal changes in selection pressure during the course of infection; frequent reversion of adaptive mutations after transmission; and the storage of the virus in the body followed by the preferential transmission of stored ancestral virus. We evaluate each of these mechanisms to determine whether they are likely to make a major contribution to the mismatch in phylogenetic rates. We conclude that the cycling of the virus through very long-lived memory CD4(+) T cells, a process that we call 'store and retrieve', is probably the major contributing factor to the rate mismatch. The preferential transmission of ancestral virus needs to be integrated into evolutionary models if we are to accurately predict the evolution of immune escape, drug resistance and virulence in HIV-1 at the population level. Moreover, early infection viruses should be the major target for vaccine design, because these are the viral strains primarily involved in transmission.
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