Necrosis of host cells and survival of pathogens following iron overload in an in vitro model of co-infection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis

ABSTRACT Quiescent T lymphocytes containing latent human immunodeficiency virus (HIV) provide a long-lived viral reservoir. This reservoir may be the source of active infection that is reinitiated following the cessation of antiretroviral therapy. Therefore, it is important to understand the mechanisms involved in latent infection to develop new strategies to eliminate the latent HIV reservoir. We have previously demonstrated that latently infected quiescent lymphocytes can be generated during thymopoiesis in vivo in the SCID-hu mouse system. However, there is still a pressing need for an in vitro model of HIV latency in primary human cells. Here, we present a novel in vitro model that recapitulates key aspects of dormant HIV infection. Using an enhanced green fluorescent protein-luciferase fusion protein-containing reporter virus, we have generated a stable infection in primary human CD4+ CD8+ thymocytes in the absence of viral gene expression. T-cell activation induces a >200-fold induction of reporter activity. The induced reporter activity originates from a fully reverse-transcribed and integrated genome. We further demonstrate that this model can be useful to study long terminal repeat regulation, as previously characterized NF-κB response element mutations decrease the activation of viral gene expression. This model can therefore be used to study intricate molecular aspects of activation-inducible HIV infection in primary cells.

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An in Vitro Model of Morphine Withdrawal Manifests the Enhancing Effect on Human Immunodeficiency Virus Infection of Human T Lymphocytes through the Induction of Substance P

American Journal Of Pathology ◽

10.2353/ajpath.2006.060358 ◽

2006 ◽

Vol 169 (5) ◽

pp. 1663-1670 ◽

Cited By ~ 8

Author(s):

Xu Wang ◽

Steven D. Douglas ◽

Jin-Song Peng ◽

Dun-Jin Zhou ◽

Qi Wan ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Lymphocytes ◽

Substance P ◽

Virus Infection ◽

Human Immunodeficiency Virus Infection ◽

In Vitro Model ◽

Enhancing Effect ◽

Immunodeficiency Virus ◽

Vitro Model

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Exposure of ichnovirus particles to digitonin leads to enhanced infectivity and induces fusion from without in an in vitro model system

Journal of General Virology ◽

10.1099/vir.0.83118-0 ◽

2007 ◽

Vol 88 (11) ◽

pp. 2977-2984 ◽

Cited By ~ 4

Author(s):

Don Stoltz ◽

Renée Lapointe ◽

Andrea Makkay ◽

Michel Cusson

Keyword(s):

Outer Membrane ◽

In Vitro Model ◽

Model System ◽

Host Cells ◽

Fusion Event ◽

Susceptible Host ◽

In Vitro Model System ◽

Vitro Model

Unlike most viruses, the mature ichnovirus particle possesses two unit membrane envelopes. Following loss of the outer membrane in vivo, nucleocapsids are believed to gain entry into the cytosol via a membrane fusion event involving the inner membrane and the plasma membrane of susceptible host cells; accordingly, experimentally induced damage to the outer membrane might be expected to increase infectivity. Here, in an attempt to develop an in vitro model system for studying ichnovirus infection, we show that digitonin-induced disruption of the virion outer membrane not only increases infectivity, but also uncovers an activity not previously associated with any polydnavirus: fusion from without.

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