Small Ruminant Lentiviruses and Cross Species Transmission
Giuseppe Bertoni and Barbara Blacklaws
from: Lentiviruses and Macrophages: Molecular and Cellular Interactions (Edited by: Moira Desport). Caister Academic Press, U.K. (2010)
The Visna-Maedi virus (VMV) and the caprine arthritis encephalitis virus (CAEV) were considered to be specific pathogens of sheep and goats, respectively. The finding that these lentiviruses frequently cross the species barrier between sheep and goats, and vice versa, has changed our view of the epidemiology of these viruses and they are now referred to as small ruminant lentiviruses (SRLV). A brief review of the molecular epidemiology of these lentiviruses will illustrate the diffusion and intermixing of these viruses in the two target species and documented cases of double infection and recombination between VMV and CAEV will be discussed. Monocytes-macrophages and dendritic cells are the main target cells of CAEV. Monocytes carrying the lentiviral provirus in their genome show little or no viral transcription. These latently infected cells are believed to function as "Trojan horses", capable of spreading the virus to different organs, while eluding the host immune response. The terminal maturation of monocytes to macrophages activates the expression of the transcription factors that, by interacting with the control elements in the viral LTRs, promote the production of infectious virus. The LTR sequences of different SRLV isolates are quite heterogeneous and may control the tissue-specific replication of these viruses and their virulence. SRLV replicate unrestrictedly and to high titers in differentiated macrophages in vitro, whereas in vivo virus replication is tightly controlled by mechanisms involving innate immunity and the adaptive immune system, and the intrinsic resistance of cells to retrovirus replication. SRLV manipulate the expression of different cytokines in infected cells and modulate the cytokine response of these cells to stimulation of the various receptors involved in recognizing pathogen associated molecular patterns (PAMPS). The genetic background of animals influences the clinical outcome of SRLV infection which, in contrast to HIV infected humans, is mainly benign in the majority of infected animals. Most animals therefore fulfill the criteria defining long-term non-progressors. Finally, the various strategies adopted by SRLV to manipulate the aforementioned immunological and non-immunological antiviral mechanisms directly influence the efficacy of vaccination strategies as documented by the paradoxical effects induced by experimental vaccines on viral load and pathological manifestations in vaccinated and challenged animals read more ...