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

Kazu Okuma, Reiko Tanaka, Tomoyuki Ogura, Mamoru Ito, Sei Kumakura, Mikiro Yanaka, Masako Nishizawa, Wataru Sugiura, Naoki Yamamoto, Yuetsu Tanaka
2008 Journal of Infectious Diseases  
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
more » ... pression 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-1 NL4-3 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.
doi:10.1086/524303 pmid:18171296 fatcat:hhab25hterb4ppastxybdzozpu