Analysis of the evolution, infectivity and antigenicity of circulating rabies virus strains

Abstract

Rabies virus has existed for thousands of years and is circulating in many species. In the present study, a total of 2896 rabies viruses isolated worldwide were phylogenetically classified into ten clusters based on the G gene sequence, and these clusters showed a close relationship with the hosts and regions that they were isolated from. Eighty-three representative G sequences were selected from ten clusters and were used to construct pseudoviruses using the VSV vector. The phylogenetic relationships, infectivity and antigenicity of the representative 83 pseudotyped rabies viruses were comprehensively analyzed. Eighty three pseudoviruses were divided into four antigentic clusters (GAgV), of which GAgV4 showed poor neutralization to all immunized sera. Further analysis showed that almost all strains in the GAgV4 were isolated from wild animals in the America, especially bats and skunks. No significant relationship in terms of phylogeny, infectivity and antigenicity was proved. Amino acid mutations at residues 231and 436 can affect the infectivity, while mutations at residues 113, 164 and 254 may affect the sensitivity to immunized animal sera, especially residue 254. We recommend close monitoring of infectivity and antigenicity, which should be more precise than simple genetic analysis.

Development of a novel bispecific antibody GR1801 for rabies

“…To evaluate the neutralizing activity of GR1801 against street RABVs circulating in recent years, we constructed a pseudovirus library of 21 circulating street RABVs from China and around the world. This included 16 street RABVs isolated from China, covering different hosts, provinces, and lineages (China I–VI; Figure 3A, Supporting Information: Table ), as well as five street RABVs worldwide with different geographical distribution, host, infectivity, and antigenicity selected according to our previous study (Supporting Information: Table ) 30 . By using the pseudovirus neutralization assay, we discovered that A2, B353, and GR1801 all exhibited excellent neutralizing activity against the 21 street RABVs, with the IC 50 mostly lower than 1 ng/mL (Figure 3B).…”

“…To evaluate the neutralizing activity of GR1801 against street RABVs circulating in recent years, we constructed a pseudovirus library of 21 S1), as well as five street RABVs worldwide with different geographical distribution, host, infectivity, and antigenicity selected according to our previous study (Supporting Information: Table S2). 30 By using the pseudovirus neutralization assay, we discovered that A2, B353, and GR1801 all exhibited excellent neutralizing activity against the 21 street RABVs, with the IC 50 mostly lower than 1 ng/mL (Figure 3B). This is comparable to the neutralization effect on the CVS-N2c strain.…”

Characterization of a human-mouse chimeric monoclonal antibody targeting rabies virus glycoprotein

“…It is therefore necessary to determine the neutralizing efficacy of 12-2A12 against street viruses isolated from different regions. According to the study of Cai et al [35] , a total of 59 street virus strains are classified into four geographic regions, including Asia, America, Africa and Europe. The neutralizing capacity of 12-2A12 against these street strains were measured by the pseudovirus neutralization system.…”

Characterization of a human–mouse chimeric monoclonal antibody targeting rabies virus glycoprotein

“…It is therefore necessary to determine the neutralizing efficacy of 12‐2A12 against street viruses isolated from different regions and host species. According to the study of Cai et al, 41 a total of 65 street virus strains are classified into four geographic regions, including Asia, America, Africa, and Europe. The neutralizing capacity of 12‐2A12 against these street strains were measured by the pseudovirus neutralization system.…”

“…According to the study of Cai et al, 41 a total of 65 street virus strains are classified into four geographic regions, including Asia, America, Africa, and Europe. The neutralizing capacity of 12-2A12 against these street strains were measured by the pseudovirus neutralization system.…”