page_title: Viral phylodynamics
section_title: Viral adaptation
hierarchical_section_title: Viral phylodynamics / Examples / Phylodynamics of HIV / Viral adaptation
context_page_description: Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viral phylogenies.
  Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts.
  Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates.
  Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another.
  Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes.
  Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes.
context_section_description: Purifying immune selection dominates evolution of HIV within hosts, but evolution between hosts is largely decoupled from within-host evolution. Immune selection has relatively little influence on HIV phylogenies at the population level for three reasons.
  First, there is an extreme bottleneck in viral diversity at the time of sexual transmission. Second, transmission tends to occur early in infection before immune selection has had a chance to operate. Finally, the replicative fitness of a viral strain (measured in transmissions per host) is largely extrinsic to virological factors, depending more heavily on behaviors in the host population. These include heterogeneous sexual and drug-use behaviors.
  There is some evidence from comparative phylogenetic analysis and epidemic simulations that HIV adapts at the level of the population to maximize transmission potential between hosts. This adaptation is towards intermediate virulence levels, which balances the productive lifetime of the host (time until AIDS) with the transmission probability per act. A useful proxy for virulence is the set-point viral load (SPVL), which is correlated with the time until AIDS. SPVL is the quasi-equilibrium titer of viral particles in the blood during chronic infection. For adaptation towards intermediate virulence to be possible, SPVL needs to be heritable and a trade-off between viral transmissibility and the lifespan of the host needs to exist.  SPVL has been shown to be correlated between HIV donor and recipients in transmission pairs, thereby providing evidence that SPVL is at least partly heritable. The transmission probability of HIV per sexual act is positively correlated with viral load, thereby providing evidence of the trade-off between transmissibility and virulence. It is therefore theoretically possible that HIV evolves to maximize its transmission potential. Epidemiological simulation and comparative phylogenetic studies have shown that adaptation of HIV towards optimum SPVL could be expected over 100–150 years. These results depend on empirical estimates for the transmissibility of HIV and the lifespan of hosts as a function of SPVL.
caption: Between-host and within-host HIV phylogenies. Sequences were downloaded from the LANL HIV sequence database. Neighbor-joining trees were estimated from Alignment1, and the within host tree is based on data from patient 2. Trees were re-rooted using Path-o-gen using known sample dates.