Macroevolution of virulence shifts in human-infective RNA virus species

Abstract

Study Objectives: To determine the frequency and distribution of virulence shifts across 40 viral genera that include human-infective RNA virus species using evolutionary discrete trait models.

Methods: An inhouse database containing RNA-dependent RNA polymerase (RdRp) gene sequences from human and non-human infective RNA virus species was updated in January – March 2021. RdRp gene sequences were obtained from NCBI GenBank for newly identified virus species. Data describing viral virulence in humans was obtained by a literature search in June 2021 and virus species were categorized as either being non-human-infective, non-severe, moderate or severe. Phylogenetic trees based on the RdRp gene sequences were estimated, discrete virulence trait evolution modelled, and discrete virulence trait transitions counted.

Results: The final dataset contained RdRp gene sequences of 579 viral species. 38.3% (222) of all viruses were human-infective of which 21.6% (48) were classified as severe, 11.7% (26) as moderate and 66.7% (148) as non-severe. The Flavivirus genus had the highest number of severe virus species (10). 83% of severe virus species or clades were likely to have evolved from non-human-infective ancestral viruses. Large virulence increases once a virus had evolved the ability to infect humans were rare as only 2 transitions from non-severe to severe were observed. Discrete trait transitions from severe to non-severe were more frequent with 10 transitions. Transition to moderate from non-severe or severe were more balanced with evidence of 8 and 4 transitions, respectively. When transitions from no-human- infective viruses to any virulence class were stratified by envelope, genome and transmission mode, no transitions to severe were found for non-enveloped, dsRNA and vector-borne viruses.

Conclusion: This study fits within a broader framework of comparative studies that attempts to understand the variation in virulence of viral genera that contain human- infective RNA viruses. The findings from this study suggest that, from a macroevolutionary viewpoint, the evolution of large virulence transitions are infrequent once RNA virus species have evolved human-infectivity.