Hepatitis C virus (HCV) is a leading worldwide cause of liver disease. Here, we use a new model of HCV spread to investigate the epidemic behavior of the virus and to estimate its basic reproductive number from gene sequence data. We find significant differences in epidemic behavior among HCV subtypes and suggest that these differences are largely the result of subtype-specific transmission patterns. Our model builds a bridge between the disciplines of population genetics and mathematical epidemiology by using pathogen gene sequences to infer the population dynamic history of an infectious disease.

Primate lentiviruses (PLV) from closely related primate species have been observed to be more closely related to each other than to PLV from more distantly related primate species. The current explanation for this observation is the codivergence hypothesis; that is, the divergence of a virus lineage results from the divergence of the host lineage. We show that, alternatively, frequent cross-species transmission of PLV, coupled with a tendency for more closely related primate species to exchange viruses “successfully,” can result in apparent codivergence. This host-switching hypothesis reconciles several puzzling observations related to the evolution of PLV.

Porcine circovirus 2 (PCV2) is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS), one of the most economically important emerging swine diseases worldwide. Virulent PCV2 was first identified following nearly simultaneous outbreaks of PMWS in North America and Europe in the 1990s and has since achieved global distribution. However, the processes responsible for the emergence and spread of PCV2 remain poorly understood. Here, phylogenetic and cophylogenetic inferences were utilized to address key questions on the time scale, processes, and geographic diffusion of emerging PCV2. The results of these analyses suggest that the two genotypes of PCV2 (PCV2a and PCV2b) are likely to have emerged from a common ancestor approximately 100 years ago and have been on independent evolutionary trajectories since that time, despite cocirculating in the same host species and geographic regions. The patterns of geographic movement of PCV2 that we recovered appear to mimic those of the global pig trade and suggest that the movement of asymptomatic animals is likely to have facilitated the rapid spread of virulent PCV2 around the globe. We further estimated the rate of nucleotide substitution for PCV2 to be on the order of 1.2 × 10 ⁻³ substitutions/site/year, the highest yet recorded for a single-stranded DNA virus. This high rate of evolution may allow PCV2 to maintain evolutionary dynamics closer to those of single-stranded RNA viruses than to those of double-stranded DNA viruses, further facilitating the rapid emergence of PCV2 worldwide.

Hantaviruses are considered one of the best examples of a long-term association between RNA viruses and their hosts. Based on the appearance of strong host specificity, it has been suggested that hantaviruses cospeciated with the rodents and insectivores they infect since these mammals last shared a common ancestor, approximately 100 million years ago. We tested this hypothesis of host–virus codivergence in two ways: 1) we used cophylogenetic reconciliation analysis to assess the fit of the virus tree onto that of the host and 2) we estimated the evolutionary rates and divergence times for the Hantavirus genus using a Bayesian Markov Chain Monte Carlo method and similarly compared these with those of their hosts. Our reconciliation analysis provided no evidence for a history of codivergence between hantaviruses and their hosts. Further, the divergence times for the Hantavirus genus were many orders of magnitude too recent to correspond with the timescale of their hosts' speciation. We therefore propose that apparent similarities between the phylogenies of hantaviruses and their mammalian hosts are the result of a more recent history of preferential host switching and local adaptation. Based on the presence of clade-defining amino acids in all genomic segments, we propose that the patterns of amino acid replacement in these viruses are also compatible with a history of host-specific adaptation.