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Journal of Virology, December 2005, p. 15038-15042, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15038-15042.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Simultaneous Mutations in CA and Vif of Maedi-Visna Virus Cause Attenuated Replication in Macrophages and Reduced Infectivity In Vivo

Bjarki Gudmundsson,1 Stefán Ragnar Jónsson,1,2 Oddur Ólafsson,1 Gudrún Agnarsdóttir,1 Sigrídur Matthíasdóttir,1 Gudmundur Georgsson,1 Sigurbjorg Torsteinsdóttir,1 Vilhjálmur Svansson,1 Helga Bryndís Kristbjornsdóttir,1 Sigrídur Rut Franzdóttir,1 Ólafur S. Andrésson,1 and Valgerdur Andrésdóttir1*

Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland,1 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota2

Received 8 July 2005/ Accepted 20 September 2005

Maedi-visna virus (MVV) is a lentivirus of sheep sharing several key features with the primate lentiviruses. The virus causes slowly progressive diseases, mainly in the lungs and the central nervous system of sheep. Here, we investigate the molecular basis for the differential growth phenotypes of two MVV isolates. One of the isolates, KV1772, replicates well in a number of cell lines and is highly pathogenic in sheep. The second isolate, KS1, no longer grows on macrophages or causes disease. The two virus isolates differ by 129 nucleotide substitutions and two deletions of 3 and 15 nucleotides in the env gene. To determine the molecular nature of the lesions responsible for the restrictive growth phenotype, chimeric viruses were constructed and used to map the phenotype. An L120R mutation in the CA domain, together with a P205S mutation in Vif (but neither alone), could fully convert KV1772 to the restrictive growth phenotype. These results suggest a functional interaction between CA and Vif in MVV replication, a property that may relate to the innate antiretroviral defense mechanisms in sheep.


* Corresponding author. Mailing address: Institute for Experimental Pathology, University of Iceland, Keldur v/Vesturlandsveg, 112 Reykjavík, Iceland. Phone: 354-5855100. Fax: 354-5673979. E-mail: valand{at}hi.is.


Journal of Virology, December 2005, p. 15038-15042, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15038-15042.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.







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