Rinderpest virus H protein: role in determining host range in rabbits

Abstract

A major molecular determinant of virus host-range is thought to be the viral protein required for cell attachment. We used a recombinant strain of Rinderpest virus (RPV) to examine the role of this protein in determining the ability of RPV to replicate in rabbits. The recombinant was based on the RBOK vaccine strain, which is avirulent in rabbits, carrying the haemagglutinin (H) protein gene from the lapinized RPV (RPV-L) strain, which is pathogenic in rabbits. The recombinant virus (rRPVlapH) was rescued from a cDNA of the RBOK strain in which the H gene was replaced with that from the RPV-L strain. The recombinant grew at a rate equivalent to the RPV-RBOK parental virus in B95a cells but at a lower rate than RPV-L. The H gene swap did not affect the ability of the RBOK virus to act as a vaccine to protect cattle against virulent RPV challenge. Rabbits inoculated with RPV-L became feverish, showed a decrease in body weight gain and leukopenia. High virus titres and histopathological lesions in the lymphoid tissues were also observed. Clinical signs of infection were never observed in rabbits inoculated with either RPV-RBOK or with rRPV-lapH ; however, unlike RPV-RBOK, both RPV-L and rRPV-lapH induced a marked antibody response in rabbits. Therefore, the H protein plays an important role in allowing infection to occur in rabbits but other viral proteins are clearly required for full RPV pathogenicity to be manifest in this species.

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

“…3). The "starry-sky" effect, which was observed in the spleens of rabbits infected with rRPV-lapH (29), was also seen in the present experiments.…”

“…Rabbits inoculated with 10 4 TCID 50 of RPV-Lv per ml became pyrexic from 1 dpi, while body weight loss and leukopenia were observed from 2 dpi. Rabbits inoculated with either rRPV-RBOK or rRPV-lapH showed no observable clinical signs of infection, as observed in our previous study (29). In contrast, rabbits inoculated with rRPV-lapPH or rRPV-lapNPH showed high fever on 2 dpi and also mild leukopenia, although body weight loss was not observed.…”

“…High virus titers, ranging from 3.0 to 4.9 log TCID 50 /ml, were detected in the mesenteric lymph nodes, superficial lymph nodes, appendices, spleens, and Peyer's patches of all rabbits inoculated with RPV-Lv. In contrast, no virus was detected in lymphoid tissues of rabbits inoculated with either rRPV-RBOK or rRPV-lapH, as previously noted (29). High virus titers were detected in all of the tissues of one rabbit inoculated with rRPV-lapPH.…”

“…The RPV-Lv strain, which is a highly virulent for rabbits and was obtained by virus cloning from the RPV-L strain (M. Shiotani et al, submitted for publication), was used in this study, along with the rRPV-RBOK virus rescued from a full-length DNA copy (cDNA) of the genome of the RBOK vaccine strain (3). Virus was also rescued from a plasmid carrying the full genome of the rRPV-RBOK virus with the H protein gene derived from RPV-Lv (rRPV-lapH) (29). This plasmid was used for constructions of full-length cDNAs in which the P gene alone or the N and P genes combined were derived from RPV-Lv.…”

“…From these incidents it is clear that a high probability of cross-species infection by paramyxoviruses exists, and so the determinants of cross-species pathogenicity following infection with these viruses should be a high priority for research. As a first step toward understanding these mechanisms, we studied the role of the hemagglutinin (H) protein gene of RPV as a pathogenic determinant in a rabbit model, since virus entry was considered one of the key elements determining cross-species infectivity (29). From these experiments it was clear that the H protein of the lapinized strain played an important role in allowing infection to occur but was not a factor determining pathogenicity for rabbits.…”