ArticleJournal of virology2000
Human immunodeficiency virus type 1 pathogenesis in SCID-hu mice correlates with syncytium-inducing phenotype and viral replication.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis.PLoS pathogens · 2021Article
- Review
- Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.Cell death & disease · 2015Review
- Viral envelope is a major determinant of enhanced fitness of a multidrug-resistant HIV-1 variant.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.Retrovirology · 2013Article
- HIV-1 induced bystander apoptosis.Viruses · 2012Review
- HIV ENV glycoprotein-mediated bystander apoptosis depends on expression of the CCR5 co-receptor at the cell surface and ENV fusogenic activity.The Journal of biological chemistry · 2011Article
- Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms.PloS one · 2010Article
- The tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope.Cell death and differentiation · 2009Article
- In vitro characterization of multidrug-resistant HIV-1 isolates from a recently infected patient associated with dual tropism and rapid disease progression.Journal of acquired immune deficiency syndromes (1999) · 2008Article
- Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.PloS one · 2008Article
- V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies.PLoS pathogens · 2007Article
- Human immunodeficiency virus persistence and production in T-cell development.Clinical and vaccine immunology : CVI · 2006Article
- Fusion-induced apoptosis contributes to thymocyte depletion by a pathogenic human immunodeficiency virus type 1 envelope in the human thymus.Journal of virology · 2006Article
- Extensive syncytium formation mediated by the reovirus FAST proteins triggers apoptosis-induced membrane instability.Journal of virology · 2005Article
- R5 human immunodeficiency virus type 1 infection of fetal thymic organ culture induces cytokine and CCR5 expression.Journal of virology · 2005Article
- Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope.Virology · 2004Article
- Induction of simian AIDS in infant rhesus macaques infected with CCR5- or CXCR4-utilizing simian-human immunodeficiency viruses is associated with distinct lesions of the thymus.Journal of virology · 2004Article
- Contrasting use of CCR5 structural determinants by R5 and R5X4 variants within a human immunodeficiency virus type 1 primary isolate quasispecies.Journal of virology · 2003Article
- HIV-1 replication and pathogenesis in the human thymus.Current HIV research · 2003Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus type 1 (HIV-1) patient isolates and molecular clones were used to analyze the determinants responsible for human CD4(+) thymocyte depletion in SCID-hu mice. Non-syncytium-inducing, R5 or R3R5 HIV-1 isolates from asymptomatic infected people showed little or no human CD4(+) thymocyte depletion in SCID-hu mice, while syncytium-inducing (SI), R5X4 or R3R5X4 HIV-1 isolates from the same individuals, isolated just prior to the onset of AIDS, rapidly and efficiently eliminated CD4-bearing human thymocytes. We have mapped the ability of one SI HIV-1 isolate to eliminate CD4(+) human cells in SCID-hu mice to a region of the env gene including the three most amino-terminal variable regions (V1 to V3). We find that for all of the HIV-1 isolates that we studied, a nonlinear relationship exists between viral replication and the depletion of CD4(+) cells. This relationship can best be described mathematically with a Hill-type plot indicating that a threshold level of viral replication, at which cytopathic effects begin to be seen, exists for HIV-1 infection of thymus/liver grafts in SCID-hu mice. This threshold level is 1 copy of viral DNA for every 11 cells (95% confidence interval = 1 copy of HIV-1 per 67 cells to 1 copy per 4 cells). Furthermore, while SI viruses more frequently achieve this level of replication, replication above this threshold level correlates best with cytopathic effects in this model system. We used GHOST cells to map the coreceptor specificity and relative entry efficiency of these early- and late-stage patient isolates of HIV-1. Our studies show that coreceptor specificity and entry efficiency are critical determinants of HIV-1 pathogenesis in vivo.
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