Skip to main content
ARS Home » Northeast Area » Orient Point, New York » Plum Island Animal Disease Center » Foreign Animal Disease Research » Research » Publications at this Location » Publication #308981

Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus(FMDV)

Location: Foreign Animal Disease Research

Title: Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions

Author
item Mohapatra, Jajati - Indian Veterinary Research Institute
item Pandey, Laxmi - Indian Veterinary Research Institute
item Rai, Devendra - Oak Ridge Institute For Science And Education (ORISE)
item Das, Biswajit - Indian Veterinary Research Institute
item Rodriguez, Luis
item Rout, Manoranjan - Indian Veterinary Research Institute
item Subramaniam, Saravanan - Indian Veterinary Research Institute
item Sanyal, Aniket - Indian Veterinary Research Institute
item Rieder, Aida - Elizabeth
item Pattnaik, Bramhadev - Indian Veterinary Research Institute

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2014
Publication Date: 3/1/2015
Citation: Mohapatra, J.K., Pandey, L.K., Rai, D.K., Das, B., Rodriguez, L.L., Rout, M., Subramaniam, S., Sanyal, A., Rieder, A.E., Pattnaik, B. 2015. Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions. Journal of General Virology. 96:553-564.

Interpretive Summary: Currently, FMDV vaccines are produced in expensive biological containment facilities where live virulent FMDV is grown in large volumes in cell cultures. In order to make vaccines, the virus needs to be adapted to grow in animal cells, which often results in changes to the virus proteins. Here we report the location and nature of changes occurring on the proteins of Indian FMDV strains during the course of cell culture adaptation. We showed that these changes in the cell-adapted viruses increased their ability of entering the cells. This information will ultimately be applied to designing better vaccine candidates with enhanced growth properties.

Technical Abstract: In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained several positively charged amino acids in the putative heparan sulfate-binding pocket (VP2 Beta E-Beta F loop, VP1 C terminus and VP3 Beta-B knob), surrounding the five-fold symmetry axis (VP1 Beta F-Beta G loop) and at other discrete sites on the capsid (VP3 Beta G-Beta H loop, VP1 C terminus, VP1 Beta G-Beta H loop and VP2 Beta C strand). A lysine insertion in the VP1 Beta F-Beta G loop of two of the BHK-21 adapted viruses supports the biological advantage of positively charged residues acquired in cell culture. The charge transitions occurred irrespective of host cell line suggesting their possible role in ionic interaction with ubiquitous negatively charged cell surface molecules such as glycosaminoglycans (GAG). This was supported by the ability of the cell culture-adapted variants to replicate in the integrin-deficient, GAG-positive CHO-K1 cells. Substitutions fixed in the VP1 Beta G-Beta H loop (negative 3, negative 2 and positive 2 ‘RGD’ positions) or in the structural element known to be juxtaposed against that loop (VP1 Beta B-Beta C loop) suggest their possible role in modulating the efficiency and specificity of interaction of ‘RGD’ motif with alpha nu-integrin receptors. The nature and location of the substitutions described in this study could be applied in the rapid cell culture adaptation of viral strains for vaccine production.