Serial infection of diverse host (Mus) genotypes rapidly impedes pathogen fitness and virulence.
Reduced genetic variation among hosts may favour the emergence of virulent infectious diseases by enhancing pathogen replication and its associated virulence due to adaptation to a limited set of host genotypes. Here, we test this hypothesis using experimental evolution of a mouse-specific retroviral pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral titre) and virulence increases when FV complex serially infects a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains modelling the diversity in natural host populations. Additionally, a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence FV complex phenotype in these experiments. The potent inhibition of viral fitness and virulence was associated with an observed loss of the defective retroviral genome (spleen focus-forming virus), whose presence exacerbates infection and drives disease in susceptible mice. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution and suggests that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals.
Department of Pathology, Division of Microbiology and Immunology, School of Medicine, University of Utah, 15 North Medical Drive East, Salt Lake City, UT 84112, USA jason.kubinak@path.utah.edu.
Jason L
JL
Kubinak
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
Douglas H
DH
Cornwall
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, USA.
Kim J
KJ
Hasenkrug
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA Department of Mathematics, University of Utah, 155 South 1400 East, Salt Lake City, UT 84112, USA.
Frederick R
FR
Adler
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
Wayne K
WK
Potts
D000818:Animals; D005075:Biological Evolution; D005260:Female; D005622:Friend murine leukemia virus / Q000472:pathogenicity* / Q000502:physiology*; D056084:Genetic Fitness; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D012192:Retroviridae Infections / Q000235:genetics* / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D014412:Tumor Virus Infections / Q000235:genetics* / Q000821:virology; D014774:Virulence / Q000502:physiology
endangered species; experimental evolution; genetic diversity; livestock; sex-against-virulence; virulence evolution