Because most studies of AIDS pathogenesis in nonhuman primates have been performed in Indian-origin rhesus macaques (Macaca mulatta), little is known about lentiviral pathogenicity and control of virus replication following infection of alternative macaque species. Here, we report the consequences of simian-human immunodeficiency virus SHIV-89.6P and SIVmac251 infection in cynomolgus (Macaca fascicularis) and rhesus macaques of Chinese origin. Compared to the pathogenicity of the same viruses in Indian rhesus macaques, both cynomolgus and Chinese rhesus macaques showed lower levels of plasma virus. By 9 to 10 months after infection, both viruses became undetectable in plasma more frequently in cynomolgus than in either Chinese or Indian rhesus macaques. Furthermore, after SHIV-89.6P infection, CD4؉ T-cell numbers declined less and survival was longer in cynomolgus and Chinese rhesus macaques than in Indian rhesus macaques. This attenuated pathogenicity was associated with gamma interferon ELISPOT responses to Gag and Env that were generated earlier and of higher frequency in cynomolgus than in Indian rhesus macaques. Cynomolgus macaques also developed higher titer neutralizing antibodies against SHIV-89.6 at 10 and 20 weeks postinoculation than Indian rhesus macaques. These studies demonstrate that the pathogenicity of nonhuman primate lentiviruses varies markedly based on the species or geographic origin of the macaques infected and suggest that the cellular immune responses may contribute to the control of pathogenicity in cynomolgus macaques. While cynomolgus and Chinese rhesus macaques provide alternative animal models of lentiviral infection, the lower levels of viremia in cynomolgus macaques limit the usefulness of infection of this species for vaccine trials that utilize viral load as an experimental endpoint.Nonhuman primates infected with naturally occurring or genetically engineered lentiviruses serve as important animal models for evaluating the efficacy of candidate AIDS vaccines (9,14). Studies in which macaques are immunized with new vaccine prototypes and subsequently challenged with pathogenic lentiviruses help to determine which vaccine products are best advanced to human clinical trials. The vast majority of AIDS vaccine/challenge data has been generated in rhesus macaques of Indian origin. An extensive knowledge of the genetics of Indian rhesus macaques has allowed detailed characterizations of major histocompatibility complex (MHC)-restricted immune responses elicited during vaccination and challenge (1, 17). However, infection of alternative macaque species such as cynomolgus or rhesus macaques from different geographic origins could provide information on comparative pathogenicity and provide an opportunity to examine diverse responses to viral infections.Rhesus macaques of Chinese origin, both wild and captive, are more plentiful than Indian origin rhesus macaques. Preliminary observations suggest that important genetic differences may exist between regional populations of rhesus macaques ...

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.

Summary Non‐human primates serve as key animal models for a variety of viral infections. To evaluate the contribution of natural killer (NK) cells to the immune‐mediated control of these viruses in macaque monkeys, we have described a method for depleting NK cells in vivo by administration of anti‐human CD16 mouse monoclonal antibody. Using a fluorometric NK‐cell cytotoxicity assay, we show that most NK‐cell cytotoxicity in rhesus monkey peripheral blood mononuclear cells resides in the CD16+ and/or CD159A+ subset of lymphocytes. The anti‐human CD16 antibody, 3G8, binds to subsets of rhesus monkey lymphocytes and monocytes but not to neutrophils. Intravenous administration of 10–50 mg/kg of 3G8 to normal rhesus monkeys resulted in anti‐CD16 antibody persistence in the plasma for 1–3 weeks. This treatment also depleted 80–90% of CD3– CD159A+ lymphocytes, putative NK cells, from blood for at least 1 week and was associated with the loss of NK‐cell cytotoxicity when evaluated by in vitro assays. Using this method, transient depletion of NK cells from two rhesus monkeys chronically infected with simian immunodeficiency virus failed to cause changes in virus replication. These studies describe a non‐human primate model for in vivo NK‐cell depletion and suggest a limited role for cytotoxic CD16+ NK cells in controlling AIDS virus replication during chronic infection.