The Reservoir for HIV-1 in Human Peripheral Blood Is a T Cell That Maintains Expression of CD4

Schnittman, S M; Psallidopoulos, Miltiades C.; Lane, H. Clifford; Thompson, L M; Baseler, Michael; Massari, F; Fox, CH; Np, Salzman; As, Fauci

doi:10.1126/science.2665081

Cited by 699 publications

(304 citation statements)

References 35 publications

Supporting

Mentioning

285

Contrasting

Unclassified

Order By: Relevance

“…The selective infection and death of CD4+ T cells provides a simple explanation for the impairment of the immune system (2,3). This explanation, however, is widely debated (4)(5)(6)(7).…”

mentioning

confidence: 99%

Diversity and virulence thresholds in AIDS

Boer¹,

Boerlijst²

1996

Models for Infectious Human Diseases

View full text Add to dashboard Cite

We propose a model for the interaction between human immunodeficiency virus and the immune system. Two differential equations describe the interactions between one strain of virus and one clone of T lymphocytes. We use the model to generalize earlier results pertaining to the AIDS diversity threshold [Nowak, M. A., Anderson, R. M., McLean The development of AIDS is associated with the selective depletion of the most crucial cell type of the immune system: the CD4+ helper T cell. The human immunodeficiency virus (HIV) infects helper T cells by binding the gpl20 virus envelope glycoprotein to CD4+ molecules (1). The selective infection and death of CD4+ T cells provides a simple explanation for the impairment of the immune system (2, 3). This explanation, however, is widely debated (4-7).One hallmark of HIV infection is the long and variable incubation period. Although the processes of infection and immune activation have a short time scale, a typical time scale for the incubation period is 10 years (8). Another hallmark of HIV is its enormous genetic diversity. The dominant surface antigen for the immune response is the V3 loop of gpl20 (9,10). This V3 loop is hypervariable: virus isolates from one infected individual have genetically different V3 loops (11, 12). Since HIV accumulates one point mutation per genome during an average replication cycle (12,13), the genetic variability will grow exponentially. However, antigenic variability is not unique to HIV: several pathogens possess antigenic variability which lets them "run ahead" of the immune response.A recent model (14-17) combines these two hallmarks of AIDS in that it attributes the long and variable incubation period to genetic variability. The authors of the model coinedThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. the term "diversity threshold" for the critical variability beyond which the immune system is no longer capable of controlling the virus. The diversity threshold emerges mathematically from their simple and quite reasonable model. The diversity threshold (14-17) is a generic property of a wide variety of models. (See refs. 17 and 18 for recent reviews of mathematical models for the various pathogenic effects of HIV.)The virus quasispecies (19) not only increases in diversity but also evolves physiologically different strains. Virus strains evolve different replication rates, cytotrophisms, and antigenicities (20)(21)(22). Here we develop a model that allows us to study the relation between the diversity of the virus quasispecies and the "virulence" of each virus strain. We derive a dimensionless virulence parameter and show that it is involved in well-known local and global bifurcations. Models of the Immune Response to HIVOur models describe the interactions between one strain of virus vj, where j is the strain number, and the clone(s) of CD4+ T cells tj that recognizes thi...

show abstract

“…The selective infection and death of CD4+ T cells provides a simple explanation for the impairment of the immune system (2,3). This explanation, however, is widely debated (4)(5)(6)(7).…”

mentioning

confidence: 99%

Diversity and virulence thresholds in AIDS

Boer¹,

Boerlijst²

1996

Models for Infectious Human Diseases

View full text Add to dashboard Cite

show abstract

“…In general agreement with this notion are a number of studies that measured the viral load in serum by quantitative virus culture or quantitative polymerase chain reaction, the number of infected cells in peripheral blood and lymph nodes by PCR or by in situ methods, and the levels of HIV antigenemia by immunologic procedures (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 88%

Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

et al. 1997

View full text Add to dashboard Cite

A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels.To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template.Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken

show abstract

“…The mechanism by which the virus causes the destruction of the CD4 T cell population is poorly understood, especially as only one in 1000 cells or fewer in peripheral blood are infected with HIV [2]. Other studies have indicated that there is a greater frequency of HIV infection in the lymphoid tissues [3,4], and that the destruction of the CD4 population cannot be attributed to viral load alone.…”

Section: Introductionmentioning

confidence: 99%

Correlation between expression of antibodies to histone H2B and clinical activity in HIV-infected individuals

Williams

Whalley

Comacchio

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYLevels of autoantibodies specific for the histone, H2B, were measured in individuals with HIV infection. In comparison with normal (uninfected) controls, infected patients, particularly those with symptomatic disease, had significantly elevated titres of anti-H2B antibodies. Longitudinal studies confirmed that levels of these antibodies were highest in patients with lymphadenopathy and declined with the development of AIDS. In preliminary experiments designed to determine the biological significance of the anti-histone antibodies, H2B was shown to be immunologically cross-reactive with an 18-kD antigen on the surface of HIV-infected or mitogen-activated CD4 cells. Protein sequencing of the 18-kD antigen has since shown complete homology with histone H2B. Because the titres of H2B autoantibodies were found to parallel the numbers of circulating CD4 cells, it is possible that these antibodies are involved in the destruction of the helper/inducer T lymphocyte population.

show abstract

The Reservoir for HIV-1 in Human Peripheral Blood Is a T Cell That Maintains Expression of CD4

Cited by 699 publications

References 35 publications

Diversity and virulence thresholds in AIDS

Diversity and virulence thresholds in AIDS

Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

Correlation between expression of antibodies to histone H2B and clinical activity in HIV-infected individuals

Contact Info

Product

Resources

About