Interleukin-4—Transgenic hu-PBL-SCID Mice: A Model for the Screening of Antiviral Drugs and Immunotherapeutic Agents against X4 HIV-1 Viruses

CXCR4-tropic (X4) human immunodeficiency virus type 1 (HIV-1) does not efficiently infect and replicate in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells, termed “hu-PBL-SCID mice,” due to, at least in part, relatively low levels of expressio...

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Bibliographic Details
Published in:The Journal of infectious diseases 2008-01, Vol.197 (1), p.134-141
Main Authors: Okuma, Kazu, Tanaka, Reiko, Ogura, Tomoyuki, Ito, Mamoru, Kumakura, Sei, Yanaka, Mikiro, Nishizawa, Masako, Sugiura, Wataru, Yamamoto, Naoki, Tanaka, Yuetsu
Format: Article
Language:English
Subjects:
Animals
Arginine - analogs & derivatives
Arginine - pharmacology
Biological and medical sciences
Cytometry
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
HIV 1
HIV Infections - drug therapy
HIV Infections - virology
HIV-1 - drug effects
HIV/AIDS
Human immunodeficiency virus 1
Humans
Infections
Interleukin-4 - genetics
Interleukin-4 - metabolism
Mice
Mice, SCID - genetics
Mice, Transgenic
Microbiology
Miscellaneous
Peritoneal lavage
Pyridines - pharmacology
Receptors
Receptors, CXCR4 - antagonists & inhibitors
Receptors, CXCR4 - genetics
Receptors, CXCR4 - metabolism
T lymphocytes
Transgenic animals
Virology
Viruses
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Summary:CXCR4-tropic (X4) human immunodeficiency virus type 1 (HIV-1) does not efficiently infect and replicate in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells, termed “hu-PBL-SCID mice,” due to, at least in part, relatively low levels of expression of the CXCR4 coreceptor. To overcome this limitation, interleukin (IL)-4-transgenic hu-PBL-SCID mice were derived that spontaneously synthesized human IL-4, which has been shown to enhance CXCR4 expression and promote X4 virus infection in vitro. Experiments reported here show that (1) synthesis of human IL-4 in vivo augmented CXCR4 expression on human CD4+ lymphocytes and importantly led to productive infection of not only X4 HIV-1NL4-3 but also multidrug-resistant primary clinical isolates and that (2) the in vivo infection could be significantly blocked by the administration of a CXCR4 antagonist. Altogether, IL-4-transgenic hu-PBL-SCID mice provide a useful model for X4 HIV-1 study and testing/screening of anti-X4 viral drugs.
ISSN:0022-1899
1537-6613
DOI:10.1086/524303