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Journal of Virology, May 2009, p. 4631-4641, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02085-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cardioviruses Are Genetically Diverse and Cause Common Enteric Infections in South Asian Children{triangledown}

Olga Blinkova,1,2 Amit Kapoor,1,2 Joseph Victoria,1,2 Morris Jones,3 Nathan Wolfe,4,5 Asif Naeem,6 Shahzad Shaukat,6 Salmaan Sharif,6 Muhammad Masroor Alam,6 Mehar Angez,6 Sohail Zaidi,6 and Eric L. Delwart1,2*

Blood Systems Research Institute, San Francisco, California,1 Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California,2 Clinical Investigation Facility, David Grant USAF Medical Center, Travis, California 94535,3 Global Viral Forecasting Initiative, San Francisco, California 94105,4 Program in Human Biology, Stanford University, Stanford, California,5 National Institute of Health, Department of Virology, Islamabad, Pakistan6

Received 3 October 2008/ Accepted 27 January 2009

Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.

* Corresponding author. Mailing address: BSRI, 270 Masonic Ave., San Francisco, CA 94118. Phone: (415) 923-5763. Fax: (415) 567-5899. E-mail: delwarte{at}medicine.ucsf.edu

{triangledown} Published ahead of print on 4 February 2009.

Journal of Virology, May 2009, p. 4631-4641, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02085-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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