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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #185761
Title: AN AGED HOST PROMOTES THE EVOLUTION OF AN AVIRULENT COXSACKIEVIRUS INTO A VIRULENT STRAIN

Author
item GAY, RAINA - TUFTS/HNRCA
item BELISLE, SARAH - TUFTS/HNRCA
item BECK, MELINDA - UNIV NO. CAROLINA-CHAPEL
item MEYDANI, SIMIN - TUFTS/HRNCA

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2006
Publication Date: 9/12/2006
Citation: Gay, R.T., Belisle, S., Beck, M.A., Meydani, S.N. 2006. An aged host promotes the evolution of an avirulent coxsackievirus into a virulent strain. Proceedings of the National Academy of Sciences. 103(37):13825-13830.

Interpretive Summary: New and more aggressive disease-causing viruses continue to emerge. It is important to learn what factors promote the evolution of such viruses. Aging, which is associated with lower resistance to viral infections, is a potential factor in viral evolution. Therefore, we chose to study a virus and any changes that might occur to it when passing it through an aged host. We infected old and young mice with a mild strain of virus named coxsackievirus (CV)B3/0 to compare the effects of infection in young versus old mice. Afterwards, we isolated the virus from the infected animals and introduced it into young mice. The mice infected with CVB3/0 that was passed through old mice showed higher viral levels in heart tissue than mice infected with the CVB3/0 that was passed through young mice. Also noted was that more deaths and greater heart disease occurred with the mice infected with CVB3/0 that was passed through old mice. Study of virus from mice infected with CVB3/0 passed through old mice showed more changes to the viral genetic makeup, which produced these harmful health effects. Our study showed that a virus that is initially not infectious or harmful can be rapidly altered into an extremely infectious, harmful form after passing through an aged host. We conclude that the aged host itself somehow promotes this change. There is a growing number of aged people in the population. The potential consequences of viral evolution predict a potential public health challenge and bears further investigation to determine more about viral evolution in the aged. Viral infection in the aged needs further study.

Technical Abstract: The emergence of new, more pathogenic viruses necessitates elucidation of factors that promote viral evolution. Aging, a potential factor, is associated with increased susceptibility to viral infections. We used a murine coxsackievirus B3 (CVB3) infection model to investigate the effects of host age on viral evolution. CVB3/0, a normally avirulent strain, was passed through an old host and the changes in pathogenicity and viral genome were examined following subsequent infection of young hosts. Mice infected with CVB3/0 that was passed through an aged host exhibited significantly higher heart viral titers, heart pathology, and mortality than mice infected with CVB3/0. Sequence analysis of virus from mice infected with CVB3/0 passed through old mice revealed 13 specific and reproducible nucleotide changes. These changes match nucleotides identified in the virulent CVB3/20 strain and are associated with cardiovirulence. However, we observed only one nucleotide change, low heart viral titers, and no heart and liver pathology in young mice infected with virus passed through a young host. This demonstrates that the aged host promotes rapid evolution of a virulent and pathogenic strain of CVB3 from an avirulent strain, and proposes a new host-virus paradigm for studies of viral infection in the aged.