Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes

Abstract

The lentiviruses of sheep, goats, and horses cause chronic multiorgan disease in which macrophages are highly permissive for viral replication. Monocytes, which mature into macrophages, are thought to be latently infected with lentivirus, but the extent to which other leukocytes are infected is unknown. Dendritic cells have not been studied separately from monocytes and T-cell subsets have not been examined in previous attempts to identify infected cells in peripheral blood mononuclear cells (PBMC). We found no evidence of T-cell tropism using an animal-passaged, pathogenic ovine lentivirus. Phytohemagglutinin-stimulated infectious PBMC produced 20-fold less virus than differentiated macrophages, and cocultivation of infectious PBMC with fresh, uninfected phytohemagglutinin blasts did not facilitate virus replication. Furthermore, central lymph cells, the best in vivo source of purified lymphocytes, lacked virus and did not yield virus upon in vitro cultivation. In contrast, cultivated blood-derived macrophages were highly permissive for viral replication. To identify the latently infected PBMC, PBMC from infected sheep were selectively depleted of monocytes and B cells by passage over nylon wool and then of nonadherent cells bearing CD4, CD8, T19, 'yb T-cell receptor, CD45RA, or major histocompatibility complex class II antigens by panning. Removal of adherent monocytes and B cells or of adherent cells and the three major T-cell subsets (CD4+, CD8+, T19+) did not decrease the infectivity of PBMC. The richest sources of infected cells in fresh PBMC were CD45RA+ and major histocompatibility complex class II+ nonadherent cells, which are three characteristics of dendritic cells. Thus, the dendritic cell, and not the monocyte or the CD4+ cell, is probably the predominant infected cell type in blood.

Common promoter deletion is associated with 3.9‐fold differential transcription of ovineCCR5and reduced proviral level of ovine progressive pneumonia virus

“…Both HIV and OPPV are macrophage‐tropic lentiviruses that cause lifelong persistent infection in the host (Gendelman et al. 1986; Gorrell et al. 1992; Thormar 2005; Alkhatib & Berger 2007).…”

Immunohistological study of the depressed cutaneous DTH response in sheep naturally infected with an ovine lentivirus (Maedi-Visna virus)

“…It is closely related biologically to lentiviruses that infect other species, including those producing immunosuppressive disease [2][3][4][5][6][7]. It differs from most of the lentiviruses in that the MVV is considered to infect solely the cells of the monocyte-macrophage series [8], contrasting with the usual concurrent lymphocyte and monocytemacrophage lentivirus infection. MVV is also unusual in that there is little evidence of clinically significant virally induced immunosuppression, and no recognized patterns of secondary infection [1,6].…”

Phenotypic analysis of cells in bronchoalveolar lavage fluid and peripheral blood of maedi visna-infected sheep

“…This finding would suggest that although lentiviruses both in humans and sheep induce inflam-matory changes by similar mechanisms, they differ in some aspects of their pathogenesis. Further investigations are required to determine if the decrease in CD4' T lymphocytes reflects an infection in some cells of this lymphocytic subset, However, recent work demonstrated that sheep lentivirus is not lymphocytotropic and does not replicate productively in CD4' T lymphocytes obtained from blood and lymph [28]. Therefore, other explanations are needed for the CD4' T cell reduction.…”