The population genetics and evolutionary epidemiology of RNA viruses

Abstract

RNA viruses are ubiquitous intracellular parasites that are responsible for many emerging diseases, including AIDS and SARS. Here, we discuss the principal mechanisms of RNA virus evolution and highlight areas where future research is required. The rapidity of sequence change in RNA viruses means that they are useful experimental models for the study of evolution in general and it enables us to watch them change in 'real time', and retrace the spread through populations with molecular phylogenies. An understanding of the mechanisms of RNA virus sequence change is also crucial to predicting important aspects of their emergence and long-term evolution.

Figure 1. Two alternative epidemiological scenarios translate into different phylogenetic tree topologies, the statistical support for which can be compared directly.

The tree in panel a depicts a common and close origin for samples 1–3 (node A), which is separate from the control samples 4–7 (node B). Node A might correspond to a single outbreak or a suspected transmission among these patients, whereas node B includes samples suspected, but not related to, the outbreak (4–7) and unrelated population controls (8,9). Panel b represents the alternative proposal for sample 1, which is now separated from the former cluster and instead groups with the control samples. Similar proposals can be separately formulated for each of the samples 1–3.

Figure 2. The phylogenetic relationships of SARS coronavirus (SARS-CoV) inferred using sequences of the spike glycoprotein.

a | Phylogenetic relationship of SARS-CoV to the known coronaviruses. Owing to the highly divergent nature of these viruses, the analysis was conducted using an alignment of 12 amino acid sequences that are 1,270 residues in length. The tree was inferred using the maximum likelihood (ML) method available in TREE-PUZZLE. Numbers next to some branches represent quartet puzzling support values, which give an indication of the reliability of that branch. SARS-CoV appears as a distinct lineage. b | Magnified phylogeny of representative SARS-CoV strains isolated from humans and the Himalayan palm civet (Paguma larvata), a putative reservoir species. The tree was constructed using the same region as in part a but using nucleotide sequences (16 sequences, 3,765 bp). The tree was inferred using the ML method available in PAUP^*. Maximum-likelihood bootstrap values are shown for the main branches. Both trees are mid-point rooted and all horizontal branches are drawn to a scale of the number of substitutions per site (note the difference in scale between the two trees). All parameter settings used in the phylogenetic analysis are available from the authors on request. The following sequences were analysed (abbreviated viral names and GenBank accession numbers are given in parentheses); Group 1 coronaviruses: feline infectious peritonitis virus (FIPV; CAA29535); Group 2 coronaviruses: bovine coronavirus (BCoV; AF220295), human coronavirus OC43 (HCoV-OC43; S44241), murine hepatitis virus (MHV; AF029248, AF201929, AF208066, CAA28484), rat sialodacryoadenitis coronavirus (SDAV; AAF97738); porcine haemagglutinating encephalomyelitis virus (PHEV; AF481863); Group 3 coronaviruses: infectious bronchitis virus (IBV; AJ311317); SARS coronaviruses: Himalayan palm civet SARS-CoV, strains SZ1 (AY304489), SZ3 (AY304486), SZ13 (AY304487) and SZ16 (AY304488), and human SARS-CoV, strains Sin2677 (AY283795), BJ01 (AY278488), CUHK-AG01 (AY345986), GD01 (AY278489), GZ02 (AY390556), GZ50 (AY304495), HSZ-Bc (AY394994), PUMC02 (AY357075), Taiwan TC1 (AY338174), TW7 (AY502930), Urbani (AY278741) and ZS-C (AY395003).