No abstract

The pathogenesis of HIV-1 infection is influenced by the immunoregulatory responses of the host. Macrophages present in the lymphoid tissue are susceptible to infection with HIV-1, but are relatively resistant to its cytopathic effects and serve as a reservoir for the virus during the course of disease. Previous investigators have demonstrated that increased serum levels of TNF-α contribute to the clinical symptoms of AIDS and that TNF-α stimulates the production of HIV-1 in chronically infected lymphocytic and monocytic cell lines by increasing HIV-1 gene expression. Although previous studies have suggested that TNF-α may increase HIV-1 infection of primary human mononuclear cells, some recent studies have indicated that TNF-α suppresses HIV-1 infection of macrophages. We now demonstrate that TNF-α suppresses HIV-1 replication in freshly infected peripheral blood monocytes (PBM) and alveolar macrophages (AM) in a dose-dependent manner. As TNF-α has been shown to increase the production of C-C chemokine receptor (CCR5)-binding chemokines under certain circumstances, we hypothesized that TNF-α inhibits HIV-1 replication by increasing the expression of these HIV-suppressive factors. We now show that TNF-α treatment of PBM and AM increases the production of the C-C chemokine, RANTES. Immunodepletion of RANTES alone or in combination with macrophage inflammatory protein-1α and -1β block the ability of TNF-α to suppress viral replication in PBM and AM. In addition, we found that TNF-α treatment reduces CCR5 expression on PBM and AM. These findings suggest that TNF-α plays a significant role in inhibiting monocytotropic strains of HIV-1 by two distinct, but complementary, mechanisms.

Wildlife restoration programs depend on having animals that have evolved to handle the constraints, including disease, posed by the new environment. Grizzly bears (Ursus arctos horribilis) once thrived while feeding on salmon (Onchorhynchus spp.) and other foods in California, Oregon, Washington, and Idaho, USA. Unlike Canadian and Alaskan salmon, salmon in lower latitudes often carry an encysted fluke (Nanophyetus salmincola) containing an endosymbiont (Neorickettsia spp.) that can produce a deadly disease in ursids and canids called salmon poisoning disease (SPD). Current recovery plans for grizzly bears in the North Cascades of Washington and the mountains of central Idaho, where infected salmon currently occur, call for using bears from several interior populations. We hypothesized that such bears with no history of salmon consumption will be sensitive to SPD. To test that idea, we fed a limited amount of fresh Chinook salmon (O. tshawytscha) harvested from rivers draining the east and west sides of the Cascades to 11 captive grizzly bears in which both parents were from populations with no history of SPD. We detected N. salmincola ova in the feces, and 8 bears exhibited typical SPD symptoms, which included decreased or no appetite, lethargy, vomiting, and diarrhea. We identified N. helminthoeca and Stellantchasmus falcatus (SF) agent (Neorickettsia sp.) in the salmon, but only SF agent occurred in the sick bears. Stellantchasmus falcatus agent is a relatively new arrival in the Pacific Northwest. Because of the severity of the disease and the potential for mortality without treatment, additional studies should be conducted to determine the distribution and prevalence of SF agent in salmon and kokanee (O. nerka) in the recovery area, develop a serum antibody test that could be used to determine exposure of bears to SF agent, and use that test to determine if grizzly bears or American black bears (U. americanus) currently living in the Pacific Northwest have been infected and recovered. If either of the latter have occurred, SPD may not prevent the successful restoration of grizzly bears where SF agent‐infected salmon will be consumed. © 2018 The Wildlife Society.