Date Published: October 13, 2016
Publisher: Public Library of Science
Author(s): Susanna K. P. Lau, Patrick C. Y. Woo, Kenneth S. M. Li, Hao-Ji Zhang, Rachel Y. Y. Fan, Anna J. X. Zhang, Brandon C. C. Chan, Carol S. F. Lam, Cyril C. Y. Yip, Ming-Chi Yuen, Kwok-Hung Chan, Zhi-Wei Chen, Kwok-Yung Yuen, Eric L Delwart.
While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing’s white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing’s white-bellied rats. While the highest prevalence was observed in Coxing’s white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses.
Picornaviruses are positive-sense, single-stranded RNA viruses with icosahedral capsids. They infect various animals and human, causing various respiratory, cardiac, hepatic, neurological, mucocutaneous and systemic diseases [1, 2]. Based on genotypic and serological characterization, the family Picornaviridae is currently divided into 29 genera with at least 50 species. Among the various picornaviruses belonging to nine genera that are able to infect humans, poliovirus and human enterovirus A71 are best known for their neurotropism and ability to cause mass epidemics with high morbidities and mortalities [3, 4]. Picornaviruses are also known for their potential for mutations and recombination, which may allow the generation of new variants to emerge [5–10].
We report the discovery of two novel rodent picornaviruses, rosavirus B and C, from six rodent species in southern China. Though being phylogenetically most closely related to Rosavirus A, “Rosavirus B” and “Rosavirus C” should represent two novel species distinct from Rosavirus A under the genus Rosavirus, according to the criteria for International Committee on Taxonomy of Viruses species demarcation for different members of Picornaviridae . Rosavirus B and C also exhibited different genome features when compared to rosavirus A. Notably, the absence of myristylation site in VP4 of rosavirus C and its varying presence in rosavirus B is intriguing. The VP4 myristylation site has been shown to play a role in localization of the capsid protein for cellular entry and permeability [43, 53]. Its absence in some rosavirus strains suggests that rosaviruses may utilize alternative strategies for capsid localization on cellular targets. In addition, the variations in Yn-Xm-AUG sequence in 5’UTR may also suggest different translational dynamics among rosaviruses. Besides phylogenetic and genomic evidence, the two viruses infect different host, with “Rosavirus B” infecting Norway rats (a street rat) and “Rosavirus C” infecting various wild rats, as supported by positive specific and/or neutralizing antibodies in the respective animals. Further studies are required to better understand the epidemiology of these novel rosaviruses in other rodent population.