title: Permissive replication of homologous murine rotavirus in the mouse intestine is primarily regulated by VP4 and NSP1.
abstract: Homologous rotaviruses (RV) are, in general, more virulent and replicate more efficiently than heterologous RV in the intestine of the homologous host. The genetic basis for RV host range restriction is not fully understood and is likely to be multigenic. In previous studies, RV genes encoding VP3, VP4, VP7, nonstructural protein 1 (NSP1), and NSP4 have all been implicated in strain- and host species-specific infection. These studies used different RV strains, variable measurements of host range, and different animal hosts, and no clear consensus on the host range restriction determinants emerged. We used a murine model to demonstrate that enteric replication of murine RV EW is 1,000- to 10,000-fold greater than that of a simian rotavirus (RRV) in suckling mice. Intestinal replication of a series of EW × RRV reassortants was used to identify several RV genes that influenced RV replication in the intestine. The role of VP4 (encoded by gene 4) in enteric infection was strain specific. RRV VP4 reduced murine RV infectivity only slightly; however, a reassortant expressing VP4 from a bovine RV strain (UK) severely restricted intestinal replication in the suckling mice. The homologous murine EW NSP1 (encoded by gene 5) was necessary but not sufficient for promoting efficient enteric growth. Efficient enteric replication required a constellation of murine genes encoding VP3, NSP2, and NSP3 along with NSP1.
authors.affiliation: Stanford University, Stanford, California, USA, and the VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Ningguo
authors.initials: N
authors.lastname: Feng
authors.forename: Linda L
authors.initials: LL
authors.lastname: Yasukawa
authors.forename: Adrish
authors.initials: A
authors.lastname: Sen
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D058507:Host Specificity; D007422:Intestines / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012401:Rotavirus / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; C060339:VP4 protein, Rotavirus; D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus