Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species

PLoS Pathogens

Andrew B. Allison¹  Alicia Ortega¹  Colin R. Parrish¹  Elizabeth A. Hoover¹  Edward C. Holmes²  Daniel M. Grove³  Dennis J. Kohler⁴ 

[1] Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America;Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia;North Dakota Game and Fish Department, North Dakota State Government, Bismarck, North Dakota, United States of America;United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Wildlife Disease Program, Fort Collins, Colorado, United States of America

关键词: Parvoviruses;    Microbial mutation;    Raccoons;    Dogs;    Carnivora;    Domestic animals;    Pets;    companion animals;    Viral packaging;   

DOI  :  10.1371/journal.ppat.1004475

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that >95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range.

【 授权许可】

CC BY