Biology and Pathogenesis of Lentiviruses (1989)

Lentiviruses are a family of retroviruses linked by similarities in genetic composition, molecular mechanisms of replication and in biological interactions with their hosts. They are best known as agents of slow disease syndromes that begin insidiously after prolonged periods of subclinical infection and progress slowly leading to the degeneration of multiple organ systems, cachexia and death. The viruses are species-specific in host range and several have been recognized as pathogens of domestic animals, non-human primates and humans. The prototypes of the family are the agents causing maedi-visna in sheep and infectious anaemia in horses. These diseases have been known for several decades and studies on the biology of the viruses have provided a fund of information that predicted most of the properties of their human counterpart which was identified only 6 years ago as the aetiological agent of AIDS. Lentiviruses persist indefinitely in their hosts and replicate continuously at variable rates during the course of the lifelong infection. Persistent replication of the viruses depends on their ability to circumvent host defences. In this respect the agents have evolved a repertoire of strategies that surpass those of any other known pathogen. Studies on immunization have shown that the viruses are poor immunogens for the induction of protective antibodies but this varies among the virus families. The ‘Achilles heel’ of these viruses lies in their absolute dependence on blood and tissue fluids for host-to-host transmission. The viruses are tropic for macrophages in vivo and replication is regulated by non-structural viral genes and by factors produced by the activated host cells. Clinical disease is related to virus replication in macrophages and two types of disease are produced: primary disease, caused directly by the lentivirus and secondary disease, caused by opportunistic agents. Primary disease is the major pathological manifestation of infection in domestic animals and is associated with the activation of virus replication in selective populations of macrophages which are tissue-specific. Host and viral factors determine which populations will be involved in the support of virus replication. Primary disease also occurs in humans and is exemplified by the unique lesions in the brain, lungs and lymph nodes of patients with AIDS and AIDS-related complex. Development of primary lesions is associated with the enhanced production of cytokines that are produced partly by the macrophage and partly by the lymphocytes, responding to antigens presented by the immunologically activated, infected macrophages. Secondary disease (AIDS) is caused by opportunistic agents which proliferate as a result of the loss of function of activated helper T lymphocytes. In humans, macaques and cats, these cells are highly susceptible to lysis by the respective viruses and/or by virus-infected macrophages under cell culture conditions. Loss of the lymphocytes in vivo leads to profound immunosuppression. Helper T lymphocytes of ungulate animals are not as sensitive to the specific lentivirus infecting the animal and this correlates with the lack of secondary diseases in these animals.