Acute Infection of Macaca nemestrina by Human Immunodeficiency Virus Type 1

Frumkin, Lyn R.; Agy, Michael B.; Coombs, Robert W.; Panther, Lori; Morton, William R.; Koehler, James K.; Florey, Mary Jo; Dragavon, Joan; Schmidt, Ann Marie; Katze, Michael G.; Corey, Lawrence

doi:10.1006/viro.1993.1392

Cited by 42 publications

(32 citation statements)

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“…Previous experiments showed that HIV-1 LA~ replicated in M. nemestrina PBMCs and purified CD4 + T cells (Agy et al, 1992;Frumkin et al, 1993). Because of the relation between neurotropism and macrophagetropism of HIV-1 isolates (see O'Brien, 1994), we performed a series of experiments to assess whether M. nemestrina primary rnonocytederived macrophages (cultured monocytes) were susceptible to in vitro infection with HIV-1La v Peripheral blood-derived monocytes were isolated by seeding 4 x 107 PBMCs from an HIV-1 antibody-negative macaque or human donor into 25 cm 2 tissue culture flasks at a concentration of 5 x 106 cells/ml macrophage medium (Macrophage-SFM; Gibco).…”

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

“…A 50% volume replacement with macrophage medium was performed every 3 days for all wells, with volume replacement of sampled culture supernatant at all sampling times. Cultured supernatants were sampled for the presence of HIV-1 antigen by whole-virus antigen capture (Frumkin et al, 1993) on days 0, 7, 14, 21 and 28 postinfection.…”

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

“…The use of macaques in this study was approved by the University of Washington Animal Care and Use Committee. Brain and deltoid muscle were obtained from four HIV-1-infected M. nemestrina [numbers 1, 2, 5 and 6 in an earlier report (Frumkin et al, 1993)] immediately after euthanasia with pentobarbital (90 mg/kg intravenously) and 60 weeks after intravenous inoculation with HIV-1LA r Macaques 1 and 2 were inoculated with a mixture of autologous PBMCs infected with HIV-1 and cell-free HIV-1 (designated cellassociated HIV-1); macaques 5 and 6 were inoculated with cell-free HIV-1 alone (see Frumkin et al, 1993). Shortly after their inoculation, all four macaques were viraemic, had HIV-1 isolated from their PBMCs and seroconverted to HIV-1.…”

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

“…All four macaques remained HIV-1 seropositive by ELISA and Western blot until necropsy at 60 weeks. However, following consistent isolation of HIV-1 by coculture during weeks 1 to 8 post-inoculation, HIV-1 was not isolated from PBMCs taken at weekly intervals from any of the animals between weeks 10 and 20 post-inoculation (Frumkin et al, 1993) or from monthly samples thereafter until the time of death. HIV-1 DNA was detected in PBMCs by PCR until week 20-22 after inoculation, and was not assessed at later times.…”

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

“…There are no published reports of virological or pathological analyses of brain from HIV-l-infected chimpanzees or gibbons, partly owing to the endangered status and limited supply of these two species. In a previous study we described six M. nemestrina that showed infection by virus recovery, seroconversion, and DNA PCR using peripheral blood mononuclear cells (PBMCs) after being intravenously inoculated with HIV-1LA I (Agy et al, 1992;Frumkin et al, 1993). In the current study we investigated for the presence of HIV-1 and pathology in the postmortem brains of four of these macaques 60 weeks after inoculation with HIV-1La v 0001-3302 © 1995 SGM…”

Section: Introductionmentioning

confidence: 98%

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Infection of Macaca nemestrina brain with human immunodeficiency virus type 1

Frumkin¹,

Patterson

Leverenz³

et al. 1995

Journal of General Virology

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We previously reported that pigtailed macaques (Macaca nemestrina) became infected after intravenous inoculation with the LAI strain of human immunodeficiency virus type 1 (HIV-1), an isolate that replicates in both M. nemestrina lymphocytes and blood-derived monocyte/ macrophages. In the current study we investigated the presence of HIV-1 and pathology in the postmortem brains of four of these macaques. Histopathological findings revealed focal lesions in white matter in the frontal and occipital lobes of one macaque, with myelin loss, nerve fibre loss, and gliosis within these lesions. Semi-quantitative, solution-based PCR revealed HIV-1 DNA in the brains of two of the other macaques. Using slide-based PCR-driven in situ hybridization, we studied these two macaques further and detected intranuclear, circular HIV-1 DNA in vascular endothelia and other non-neuronal brain cells. These findings indicate that M. nemestrina brain can be infected with HIV-1 in vivo and may provide a useful animal model for understanding early HIV-1 brain infection in humans.

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Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

Section: In Vitro Infection Of M Nemestrina Cultured Rnonocytes Withmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Infection of Macaca nemestrina brain with human immunodeficiency virus type 1

Frumkin¹,

Patterson

Leverenz³

et al. 1995

Journal of General Virology

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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Lentivirus AIDS Models

Voevodin¹,

Marx

2009

Simian Virology

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Acute Infection of Macaca nemestrina by Human Immunodeficiency Virus Type 1

Cited by 42 publications

References 0 publications

Infection of Macaca nemestrina brain with human immunodeficiency virus type 1

Infection of Macaca nemestrina brain with human immunodeficiency virus type 1

Nonhuman Primate Models for HIV/AIDS Vaccine Development

Lentivirus AIDS Models

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