Drivers of within-host genetic diversity in acute infections of viruses

PLoS Pathog. 2020 Nov 4;16(11):e1009029. doi: 10.1371/journal.ppat.1009029. eCollection 2020 Nov.


Genetic diversity is the fuel of evolution and facilitates adaptation to novel environments. However, our understanding of what drives differences in the genetic diversity during the early stages of viral infection is somewhat limited. Here, we use ultra-deep sequencing to interrogate 43 clinical samples taken from early infections of the human-infecting viruses HIV, RSV and CMV. Hundreds to thousands of virus templates were sequenced per sample, allowing us to reveal dramatic differences in within-host genetic diversity among virus populations. We found that increased diversity was mostly driven by presence of multiple divergent genotypes in HIV and CMV samples, which we suggest reflect multiple transmitted/founder viruses. Conversely, we detected an abundance of low frequency hyper-edited genomes in RSV samples, presumably reflecting defective virus genomes (DVGs). We suggest that RSV is characterized by higher levels of cellular co-infection, which allow for complementation and hence elevated levels of DVGs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytomegalovirus / genetics*
  • Cytomegalovirus Infections / virology*
  • Genetic Variation*
  • Genotype
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • Humans
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Viruses / genetics*

Grant support

This work was supported by the SAIA foundation [to MG]; by the Israeli Science Foundation [1333/16 to AS]; by the German Israeli Foundation [I-1096-411.8-2015 to AS]; by the United-States-Israel Binational Science Foundation [2016555 to AS]; by the National Science Foundation [1655212 to PSP]; by the Edmond J. Safra center for bioinformatics in Tel Aviv University [to MG, SH, TK]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.