A lentivirus-induced immunodeficiency disease in the laboratory mouse would be a boon in the fight against human AIDS, and this project will examine the wild mice most likely to have such infections. The best place to find mice with lentivirus infections is in their native rather than in their introduced range (i.e. in Europe rather than in Norther America), or in areas where natural infections with lentiviruses have already been found(i.e. in Africa). This search for murine lentiviruses in animals from these two areas uses the best available method for detecting uncharacterized viruses: lentivirus-specific oligonucleotide primers and the polymerase chain reaction (PCR) technique. Oligonucleotide primers will be designed complementary to amino acids of the pl gene region that are conserved in the lentiviruses and are different in other retroviruses. DNA preparations from frozen tissues of about 750 wild-caught Mus and other murid rodents will be screened with the lentivirus-specific probes for signs of proviral infection. To pass the first test as a new lentivirus, the amplified fragments of provirus DNAs will be sequenced and compared for their close phylogenetic relationship to known lentiviruses. Additional molecular characterization will begin by cloning the entire provirus into phage vectors. Sequencing the lentivirus- unique fiv region will be done. More animals from the infected populations will be collected and used in the laboratory. Signs of pathology will be watched for in the native hosts, in laboratory mice, and in other species of Mus that are inoculated with living virus. The range of host cells into which the virus can be infected or transfected will be studied. This will include mouse and human T-lymphocytes and other types of mouse cells. The potential of the newly discovered viruses as AIDS models will be evaluated, and infected mice or cell cultures will be provided to other researchers for further testing and use in AIDS research.
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