Rinderpest Virus Phosphoprotein Gene Is a Major Determinant of Species-Specific Pathogenicity

Abstract

We previously demonstrated that the rinderpest virus (RPV) hemagglutinin (H) protein plays an important role in determining host range but that other viral proteins are clearly required for full RPV pathogenicity to be manifest in different species. To examine the effects of the RPV nucleocapsid (N) protein and phosphoprotein (P) genes on RPV cross-species pathogenicity, we constructed two new recombinant viruses in which the H and P or the H, N, and P genes of the cattle-derived RPV RBOK vaccine were replaced with those from the rabbit-adapted RPV-Lv strain, which is highly pathogenic in rabbits. The viruses rescued were designated recombinant RPV-lapPH (rRPV-lapPH) and rRPV-lapNPH, respectively. Rabbits inoculated with RPV-Lv become feverish and show leukopenia and a decrease in body weight gain, while clinical signs of infection are never observed in rabbits inoculated with RPV-RBOK or with rRPV-lapH. However, rabbits inoculated with either rRPV-lapPH or rRPV-lapNPH became pyrexic and showed leukopenia. Further, histopathological lesions and high virus titers were clearly observed in the lymphoid tissues from animals infected with rRPV-lapPH or rRPV-lapNPH, although they were not observed in rabbits infected with RPV-RBOK or rRPV-lapH. The clinical, virological, and histopathological signs in rabbits infected with the two new recombinant viruses did not differ significantly; therefore, the RPV P gene was considered to be a key determinant of cross-species pathogenicity.Rinderpest virus (RPV) is a single-stranded, negative-sense RNA virus classified in the genus Morbillivirus in the family Paramyxoviridae, order Mononegavirales. RPV is antigenically closely related to other members of this genus, which include human measles virus (MV), peste des petits ruminants virus in sheep and goats, canine distemper virus (CDV), and phocid distemper virus, which cause diseases in carnivore species, including seals. Since the late 1980s, novel CDV and related morbillivirus infections have occurred worldwide and have caused fatal disease in several species previously considered immune to these viruses, including hyenas and various marine mammals (5, 6). Two recent CDV epidemics in large cats have been reported, one in California and the other in the Serengeti, Tanzania (1, 25a). Both were characterized by significant fatality rates (23 and 30%, respectively). Recently, two new emerging paramyxoviruses that were identified in cases of severe respiratory and encephalitic diseases in animals and humans have been described; they are now known as Hendra virus (HeV) and Nipah virus (NiV) (12). Hendra virus emerged in 1994 and was transmitted to humans by close contact with horses; Nipah virus emerged in 1999 and was passed from pigs to humans. Both are unusual among the paramyxoviruses in their abilities to infect and cause potentially fatal disease in a number of host species, including humans, although their natural host is the fruit bat. From these incidents it is clear that a high probability of cross-species infection by par...

Establishment of a Nipah virus rescue system

“…In addition to these aspects, it will be interesting to determine which viral factors are responsible for the increase in virulence when the virus crosses the species barrier as revealed in our previous studies with morbilliviruses (39,40).…”

Characterization of the complete genomic sequence of the rinderpest virus Fusan strain cattle type, which is the most classical isolate in Asia and comparison with its lapinized strain

“…These results suggest that the P, C, and V genes of RPV contribute for its pathogenicity to cattle. The P gene of RPV is believed to be a key determinant of cross-species pathogenicity [20]. The C and V proteins of morbilliviruses are not essential for replication in tissue culture cells but are known to be virulence determinants through their ability to counteract the innate immune responses to viral infection [7,[21][22][23][24].…”

Evaluation of a recombinant measles virus expressing hepatitis C virus envelope proteins by infection of human PBL-NOD/Scid/Jak3null mouse

“…We used replicationcompetent MV-based vectors (pMV; Edmonston B strain of MV) [25]. The E1 and E2 cDNAs were cloned into the Fse I site of pMV and the resulting clone, pMV-E1E2, was used to rescue the infectious recombinant MV expressing the HCV envelope glycoproteins (rMV-E1E2), as reported previously [30].…”