Insights into the biologic characteristics of lentivirus infections have been gained from experimental infections, including sheep with visna virus (Table 1). Natural disease patterns vary among species, but certain common features are recognized.
1. Viruses are transmitted by exchange of body fluids.
2. Virus persists indefinitely in infected hosts, although it may be present at very low levels.
3. Viruses have high mutation rates, and different mutants will be selected under different conditions (host factors, immune responses, tissue types). Infected hosts contain “swarms” of closely related viral genomes, known as quasispecies.
4. Virus infection progresses slowly through specific stages. Cells in the macrophage lineage play central roles in the infection. Lentiviruses differ from other retroviruses in that they can infect nondividing, terminally differentiated cells. However, those cells must be activated before viral replication ensues and progeny virus is produced. Virus is cell associated in monocytes and macrophages, but only about one cell per million is infected. Monocytes carry the virus around the body in a form that the immune system cannot recognize, seeding other tissues. Lymphocyte-tropic strains of virus tend to cause highly productive infections, whereas replication of macrophage-tropic virus is restricted.
5. It may take years for disease to develop. Infected hosts usually make antibodies, but they do not clear the infection, so virus persists lifelong. New antigenic variants periodically arise in infected hosts, with most mutations occur ring in envelope glycoproteins. Clinical symptoms may develop at any time, but chronic disease typically manifests after months to years of infection. The exceptions to long incubation periods for lentivirus disease include AIDS in children, infectious anemia in horses, and encephalitis in young goats.
Table1. Representative Members of the Lentivirus Genus
Host factors important in pathogenesis of disease include age (the young are at greater risk), stress (may trigger disease), genetics (certain breeds of animals are more susceptible), and concurrent infections (may exacerbate disease or facilitate virus transmission).
The diseases in horses, sheep, and goats are not complicated by opportunistic secondary infections. Equine infectious anemia virus can be spread among horses by bloodsucking horseflies, the only lentivirus known to be transmitted by an insect vector.
Simian lentiviruses share molecular and biologic characteristics with HIV and cause an AIDS-like disease in rhesus macaques. The SIV model is important for understanding disease pathogenesis and developing vaccine and treatment strategies.
