Simian Immunodeficiency Virus Burden in Tissues and Cellular Compartments during Clinical Latency and AIDS

Abstract

In the course of human immunodeficiency virus infection or of the related simian immunodeficiency virus (SIV), progression to AIDS is associated with high virus burdens in blood. How virus burden in the bloodstream is related to virus burden in tissue reservoirs was addressed in an animal model of rhesus macaques infected with SIV. In situ hybridization and quantitative image analysis were used to quantitate virus burden. Animals who developed AIDS had high levels of virus production and storage in lymphoid tissue reservoirs and evidence of productive infection of macrophages in the nervous system. With the quantitative approach described, it should be possible to design and assess the impact of treatment and shed light on the outstanding issues in pathogenesis.

The SIV-infected rhesus monkey model for HIV-associated dementia and implications for neurological diseases

“…The decline in the CD4/CD8 ratio appeared unrelated to the occurrence of impairment on the different tasks ( Table 2) [42]. SIV-infected animals displayed an elevation in serum p26 antigen levels within 1 month of inoculation, although to variable degrees [42,43]. Elevated plasma viral load was associated with advanced disease (Table 2) but unrelated to the onset of impairments.…”

The Effects of HIV-1 Infection on Latent Tuberculosis

“…It makes sense that the lung becomes a site of infection as all blood passes through the lung to become oxygenated and thus lung tissue is highly vascularized. In some studies, the lung has been shown to be a place of active viral replication [45] [19]. Thus, the interaction with Mtb and HIV-1 in the lung may play a role in co-infection dynamics.…”

“…We choose to model the dynamics of immune cells and pathogens in the lung as this is the primary site of infection for Mtb and there is evidence that the lungs are an important site for HIV-1 infection due to its highly vascular structure [45]. There is also evidence in non-human primate models of SIV infection indicating that HIV-1 is present there [19].…”

Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-γ in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome

“…Tissues were fixed in fresh 4% paraformaldehyde and phosphate-buffered saline and processed as described previously. 8,9 DNA array hybridization and analyses Total RNAs were extracted from snap-frozen spleen tissue homogenized in Trizol (Life Technologies, Carlsbad, CA). Equivalent masses of total RNA were combined from individual macaques to generate pools of RNA from animals with the same disease states.…”

“…ISHs were done as described previously, 8,9 except that tissue pretreatments consisted of microwaving in 0.01 M citrate buffer (pH 6.0) followed by acetylation in 0.25% acetic anhydride and 0.1 M triethanolamine and hybridization was done at 50°C. ISHs simultaneously using sulfur 35 ( 35 S)-labeled and digoxigenin 11-uridine triphosphate-labeled probes were done identically, except that all dithiothreitol (DTT) concentrations were 10 mM.…”