Drivers of within-host genetic diversity in acute infections of viruses
| Autor: | Dana G. Wolf, Pleuni S. Pennings, Michal Mandelboim, Maoz Gelbart, Talia Kustin, Adi Stern, Sheri Harari, Ya'ara Ben-Ari, Orna Mor |
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| Rok vydání: | 2020 |
| Předmět: |
RNA viruses
Heredity Pulmonology viruses Cytomegalovirus Population genetics Artificial Gene Amplification and Extension HIV Infections Pathology and Laboratory Medicine Polymerase Chain Reaction Genome Defective virus Medical Conditions Immunodeficiency Viruses Genotype Medicine and Health Sciences Biology (General) Genetics 0303 health sciences Microbial Genetics respiratory system Respiratory Syncytial Viruses Genetic Mapping Infectious Diseases Medical Microbiology Viral Pathogens Viruses Cytomegalovirus Infections RNA Viral Pathogens Research Article QH301-705.5 Immunology Respiratory Syncytial Virus Infections Biology Research and Analysis Methods Microbiology Virus Respiratory Disorders 03 medical and health sciences Virology Retroviruses Genetic variation Humans Molecular Biology Techniques Microbial Pathogens Molecular Biology 030304 developmental biology Evolutionary Biology Genetic diversity Population Biology 030306 microbiology Lentivirus Organisms Biology and Life Sciences HIV Genetic Variation RC581-607 Haplotypes Respiratory Infections HIV-1 Microbial genetics Parasitology Immunologic diseases. Allergy Population Genetics |
| Zdroj: | PLoS Pathogens, Vol 16, Iss 11, p e1009029 (2020) PLoS Pathogens |
| ISSN: | 1553-7374 |
| Popis: | 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. Author summary The few days or weeks following infection with a virus, termed acute infection, are critical for virus establishment. Here we sought to characterize what leads to differences in the genetic diversity of different viruses sampled during acute infection. We performed ultra-deep sequencing of hundreds to thousands viral genomes from forty-three samples spanning three pathogenic human viruses: HIV, RSV and CMV. We found major differences in the genetic diversity of these different viruses, and in different patients infected with the same virus. We investigated the factors responsible for these differences. We found that the DNA virus CMV was less diverse, most likely since it has a lower mutation rate than the RNA viruses HIV and RSV. We also found that the samples with the highest genetic diversity, which included one CMV sample and two HIV samples, bore evidence for multiple genotype infection. In other words, patients from whom these samples were taken were infected with two different “strains” of the virus. Finally, we also found evidence that viral genomes of HIV, and in particular RSV, are edited by the innate immune system of the host, leading to the presence of defective virus genomes. |
| Databáze: | OpenAIRE |
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