Redistribution of HIV outside the lymphoid system with onset of AIDS

Donaldson, Y K; Bell, Jeanne E.; Ironside, James W.; Brettle, R P; Robertson, J. Roy; Busuttil, A.; Simmonds, Peter

doi:10.1016/s0140-6736(94)91222-x

Cited by 90 publications

(57 citation statements)

References 22 publications

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“…In this regard, an analysis of HIV-1 decay, after the institution of highly active antiretroviral therapy in patients with moderately low CD4 ϩ T cell numbers (mean cell counts of 212 per l), indicated that 1-7% of the plasma virus was produced by long-lived infected cells, putatively defined as tissue macrophage (43). At much later times, when CD4 ϩ T cell levels in AIDS patients fall to the same range (Ͻ50 cells per l) observed in SHIV DH12R -infected rhesus monkeys, HIV-1 also becomes detectable in several nonlymphoid organs such as lung, colon, brain, liver, and kidney (44,45). In addition, the coexistence of opportunistic infections has also been reported to greatly augment both the number of productively HIV-1-infected monocyte͞ macrophage and viral RNA copies per cell (24).…”

Section: Discussionmentioning

confidence: 98%

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

Igarashi¹

2001

Proceedings of the National Academy of Sciences

203

225

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The highly pathogenic simian immunodeficiency virus͞HIV type 1 (SHIV) chimeric virus SHIV DH12R induces a systemic depletion of CD4 ؉ T lymphocytes in rhesus monkeys during the initial 3-4 weeks of infection. Nonetheless, high levels of viral RNA production continue unabated for an additional 2-5 months. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver, and kidney sustain high plasma virus loads in the absence of CD4 ؉ T cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV DH12R infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virus in vivo. They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection.

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Section: Discussionmentioning

confidence: 98%

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

Igarashi¹

2001

Proceedings of the National Academy of Sciences

203

225

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“…In vitro tests have shown that zidovudine is ineffective against chronically infected monocyte cultures (Crowe et al, 1989) and this might be due to inefficient phosphorylation (Hao et al, 1988;Balzarini et al, 1988). The patient described here received therapy at the terminal stages of disease, and as dissemination of virus to the central nervous system occurs late in infection (Donaldson et al, 1994), initiation of therapy earlier in the disease course might result in the the appearance of resistant genotypes in the brain. Finally, the possibility exists that resistance might be conferred by mutations at amino acids other than the five identified positions (Sheehy & Desselberger, 1993).…”

Section: Analyses Of R T Coding Regionsmentioning

confidence: 96%

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Sheehy

Desselberger²,

Whitwell³

et al. 1996

Journal of General Virology

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Nucleotide sequences of regions of the envelope (env) and polymerase (po/) genes of human immunodeficiency virus type 1 (HIV-1) proviral DNA were obtained from sequential blood and autopsy samples from an AIDS patient who had been treated with zidovudine for 9 months, Phylogenetic analyses showed that a reduction in genetic heterogeneity of the env regions of viruses present in the proviral blood population occurred during therapy, and this coincided with an increased pol gene heterogeneity. Differences were observed in different organs obtained post mortem for both the env and pol coding regions. The cardiac blood proviral population consisted mainly of variants which possessed sequences containing mutations at position 215 of the pol gene, associated with drug resistance. By contrast, the brain population consisted entirely of zidovudine sensitive genotypes, and this organ also harboured variants with genetically distinct env sequences. The lymph tissues obtained after death held more diverse proviral env and pol populations, containing both zidovudine sensitive and resistant genotypes.

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“…Differences in selective pressures imposed by the immune system and disparities in local concentrations of antiviral drugs can result in divergent evolution of the virus (58,61). Furthermore, compartmentalized viral populations have been shown to possess distinct phenotypic characteristics, such as cellular tropism (68), drug resistance (58,64,69), and level of pathogenesis (14).…”

mentioning

confidence: 99%

Comparative Study of Methods for Detecting Sequence Compartmentalization in Human Immunodeficiency Virus Type 1

Zárate

Pond

Shapshak

et al. 2007

J Virol

119

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Human immunodeficiency virus (HIV) infects different organs and tissues. During these infection events, subpopulations of HIV type 1 (HIV-1) develop and, if viral trafficking is restricted between subpopulations, the viruses can follow independent evolutionary histories, i.e., become compartmentalized. This phenomenon is usually detected via comparative sequence analysis and has been reported for viruses isolated from the central nervous system (CNS) and the genital tract. Several approaches have been proposed to study the compartmentalization of HIV sequences, but to date, no rigorous comparison of the most commonly employed methods has been made. In this study, we systematically compared inferences made by six different methods for detecting compartmentalization based on three data sets: (i) a sample of 45 patients with sequences gathered from the CNS, (ii) sequences from the female genital tract of 18 patients, and (iii) a set of simulated sequences. We found that different methods often reached contradictory conclusions. Methods based on the topology of a phylogenetic tree derived from clonal sequences were generally more sensitive in detecting compartmentalization than those that relied solely upon pairwise genetic distances between sequences. However, as the branching structure in a phylogenetic tree is often uncertain, especially for short, low-diversity, or recombinant sequences, tree-based approaches may need to be modified to take phylogenetic uncertainty into account. Given the frequently discordant predictions of different methods and the strengths and weaknesses of each particular methodology, we recommend that a suite of several approaches be used for reliable inference of compartmentalized population structure.

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Redistribution of HIV outside the lymphoid system with onset of AIDS

Cited by 90 publications

References 22 publications

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Comparative Study of Methods for Detecting Sequence Compartmentalization in Human Immunodeficiency Virus Type 1

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