Genetic Analysis of Phosphoprotein and Matrix Protein of Rabies Viruses Isolated in Brazil

Abstract

ABSTRACT. To investigate the genetic characteristics of phosphoprotein (P) and matrix protein (M) genes of variable rabies virus (RV) prevalent in Brazil, the authors genetically characterized the P and M genes from 30 Brazilian RV field isolates. Phylogenetic analysis based on the P and M genes revealed the presence of six RV variants that consisted primarily of three insectivorous bats, the vampire bat, dog and fox in Brazil. Specific amino acid substitutions corresponding to these phylogenetic lineages were observed, with Asp 42 and Glu 62 in the P protein found to be characteristic of Brazilian chiroptera-and carnivora-related RVs, respectively. Amino acid sequence motifs predicted to associate with a viral function in the P and M proteins were conserved among Brazilian RV variants. KEY WORDS: Brazil, genetic analysis, matrix protein, phosphoprotein, rabies virus.J. Vet. Med. Sci. 69(11): 1145-1154 Rabies virus (RV) is a member of the Lyssavirus genus, which belongs to the Rhabdoviridae family. Lyssavirus is characterized as having seven genotypes (GTs) comprising, rabies virus (GT 1), Lagos bat virus (GT 2), Mokola virus (GT 3), Duvenhage virus (GT 4), European bat lyssavirus type (EBL) 1 (GT 5), EBL 2 (GT 6) and Australian bat lyssavirus (GT 7). Lyssaviruses have approximately 12-kb of unsegmented negative-stranded genomic RNA for encoding the genes of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L).RV has an almost global distribution and infects a wide range of mammalian species in which it causes a lethal form of encephalopathy. In Brazil, the principal RV transmitters to humans and domestic animals -dogs and vampire batshave caused serious problems in the public health sector and the livestock industry [6,19]. In addition, RVs have been isolated from other animal species [8]. Previously, phylogenetic analyses targeting the N and G genes revealed that there were several RV variants which varied depending on the host species, which included vampire bats, insectivorous bats, dogs and foxes. Furthermore, RV isolates from cattle and frugivorous bats (Artibeus (A.) sp.) have frequently been typed as vampire bat-related RVs in Brazil [19,25,26,41,42,44,45]. Variability has also been reported in the G protein, a major contributor to the pathogenicity of the virus, in which several amino acid substitutions at antigenic sites associated with the pathogenicity and immunogenicity of the virus have been identified in Brazilian RV variants [41]. However, differences in the pathogenicity and antigenic characteristics of these Brazilian RV variants are not yet known. Recently, in addition to the G protein, both P and M proteins have also been reported to be associated with the pathogenicity of the virus [43]. The P protein forms a ribonucleoprotein (RNP) with N and L proteins, which then wraps around the viral RNA, and plays an important role in transcription and replication in conjunction with the L protein [3,5,11]. In addition, the P protein acts to counteract the ...

Determination and Molecular Analysis of the Complete Genome Sequence of Two Wild-Type Rabies Viruses Isolated from a Haematophagous Bat and a Frugivorous Bat in Brazil

“…The proline-rich motif of M, which is involved in viral budding and interacts with WW domains of cellular components, was conserved [10,11,13].…”

“…Complete genome lengths were different between BR-DR1 and BR-AL1 isolates, the difference in length resulting from differences in the P-M intergenic region; in contrast, the length of each ORF and each intergenic region, excluding P-M, corresponded exactly between the BR-DR1 and BR-AL1 isolates. The length of P gene sequences differed from those in fixed strains because Brazilian fox RABVs and Canadian raccoon RABV isolates were substituted at the end of the P gene [13,30]. The G-L intergenic region of the BR-DR1 and BR-AL1 isolates was the longest intergenic region, consisting of 515 nt; in contrast, the BR-Pfx1 isolate consisted of a 520 nt G-L intergenic region.…”

Molecular characterization of rabies virus isolated from non-haematophagous bats in Brazil

“…All samples belonged to the Lyssavirus genus, Rabies virus species. The reconstruction of the phylogenetic tree, with samples from the studied region, demonstrated that all segregated with samples available at GenBank and representative of genetic lineages related to bats species already identified [24][25][26][27] . The observed clusters were supported by high bootstrap values (91% to 100%).…”

Roles of the Rabies Virus Phosphoprotein Isoforms in Pathogenesis

“…While P1 physically interacts with L protein by its N-terminal domain (amino acids 1 to 19) (14) to act as a cofactor of viral RNA polymerase, tPs lack the L protein-binding domain, indicating that tPs do not have cofactor activity. Importantly, start codons for the translation of tPs are highly conserved among RABV strains (15,16), strongly suggesting a critical role of tPs in RABV infection.…”