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Molecular basis of organ-specific selection of viral variants during chronic infection

Ahmed, Rafi and Hahn, Chang S. and Somasundaram, T. and Villarete, Lorelie and Matloubian, Mehrdad and Strauss, James H. (1991) Molecular basis of organ-specific selection of viral variants during chronic infection. Journal of Virology, 65 (8). pp. 4242-4247. ISSN 0022-538X. PMCID PMC248861.

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Viral variants of different phenotypes are present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the Armstrong strain of lymphocytic choriomeningitis virus. The CNS isolates are similar to the parental virus and cause acute infections in adult mice, whereas the lymphoid isolates cause chronic infections associated with suppressed T-cell responses. In this study, we provide a molecular basis for this organ-specific selection and identify a single amino acid change in the viral glycoprotein that correlates with the tissue specific selection and the persistent and immunosuppressive phenotype of the variants. This phenylalanine (F)-to-leucine (L) change at position 260 of the viral glycoprotein was seen in the vast majority (43 of 47) of the lymphoid isolates, and variants with L at this residue were selected in spleens of persistently infected mice. In striking contrast, isolates with the parental sequence (F at residue 260) predominated (48 of 59 isolates) in the CNS of the same carrier mice. Complete nucleotide sequence analysis of the major structural genes of several independently derived (from different mice) spleen isolates showed that these variants were greater than 99.8% identical to the parental virus. In fact, the only common change among these spleen isolates was the F----L mutation at residue 260 of the glycoprotein. These results show that an RNA virus can exhibit minimal genetic drift during chronic infection in its natural host, and yet a single or few mutations can result in the organ-specific selection of variants that are markedly different from the parental virus.

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Additional Information:Copyright © 1991, American Society for Microbiology Received 7 December 1990/Accepted 1 May 1991 We thank Rita J. Concepcion for excellent technical assistance and Janna Weimer for help in preparing the manuscript. This work was supported by Public Health Service grants from the National Institutes of Health (NS-21496 to R.A. and A1-10793 to J.H.S.). R.A. is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society. M.M. was supported by NIH grant GM 08042-08, and L.V. was supported by grant CA 09120-16.
Funding AgencyGrant Number
NIHNS 21496
NIHAI 10793
National Multiple Sclerosis SocietyUNSPECIFIED
NIHGM 08042-08
NIHCA 09120-16
Issue or Number:8
PubMed Central ID:PMC248861
Record Number:CaltechAUTHORS:AHMjvir91
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2140
Deposited By: Archive Administrator
Deposited On:11 Mar 2006
Last Modified:02 Oct 2019 22:50

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