Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India

Authors: BISWAL, JITENDRA - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; RANJAN, RAJEEV - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; SUBRAMANIAM, SARAVANAN - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; MOHAPATRA, JAJATI - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; SHARMA, MUKESH - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; BERTRAM, MIRANDA - Orise Fellow; BRITO, BARBARA - Orise Fellow; Rodriguez, Luis; PATTNAIK, BRAMHADEV - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; Arzt, Jonathan

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2019
Publication Date: 6/21/2019
Citation: Biswal, J.K., Ranjan, R., Subramaniam, S., Mohapatra, J.K., Sharma, M.K., Bertram, M.R., Brito, B., Rodriguez, L.L., Pattnaik, B., Arzt, J. 2019. Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India. bioRxiv. https://doi.org/10.1371/journal.pone.0214832.
DOI: https://doi.org/10.1371/journal.pone.0214832

Interpretive Summary: Foot and mouth disease (FMD), caused by FMD virus (FMDV), is an important livestock disease that causes substantial animal health problems and economic losses in many countries in Africa and Asia, where the disease exists. Over half of FMDV-infected cattle and buffalo become persistently infected carriers, meaning the virus can be detected for 28 days or more after infection. Transmission of FMDV from carrier cattle or Asian buffalo has not been proven, however there is concern that evolution of the virus within carrier animals could lead to new, distinct strains which could cause new outbreaks of the disease. The purpose of this study was to investigate FMDV evolution within carrier cattle and Asian buffalo over a 1-year period following an outbreak at a large dairy farm in India. The report describes that the proportion of carrier animals decreased steadily over the course of the study. Genetic analysis of viruses indicated that all of the viruses obtained from carrier animals during the study originated from the outbreak virus. Additionally, variation of virus proteins fluctuated, suggesting that infected animals’ immune systems may not fully protect animals against some of the new carrier-derived viruses. However, transmission of a carrier virus to naïve animals was not observed. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV and contributes to protecting cattle in the USA, in the event of an outbreak.

Technical Abstract: The role of foot-and-mouth disease virus (FMDV) persistently infected ruminants in initiating new outbreaks remains controversial, and the perceived threat posed by such animals hinders international trade in FMD-endemic countries. In this study we report longitudinal analyses of genetic and antigenic variations of FMDV serotype O/ME-SA/Ind2001d sublineage during naturally occurring, persistent infection in cattle and buffalo at an organized dairy farm in India. The proportion of animals from which FMDV RNA was recovered was not significantly different between convalescent (post-clinical) and sub-clinically infected animals or between cattle and buffalo across the sampling period. However, infectious virus was isolated from a higher proportion of buffalo samples and for a longer duration compared to cattle. Analysis of the P1 sequences from recovered viruses indicated fixation of mutations at the rate of 1.816 x 10-2 substitution/site/year (s/s/y) (95% CI 1.362-2.31 x 10-2 s/s/y). However, the majority of point mutations were transitional substitutions. Within individual animals, the mean dN/dS (') value for the P1 region varied from 0.076 to 0.357, indicating the selection pressure acting on viral genomes differed substantially across individual animals. Statistical parsimony analysis indicated that all of the virus isolates from carrier animals originated from the outbreak virus. The antigenic relationship value as determined by 2D-VNT assay revealed fluctuation of antigenic variants within and between carrier animals during the carrier state. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV.