A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression.
A human immunodeficiency virus (HIV) type 1-transgenic mouse line (166) that previously showed up-regulated expression of viral proteins and infectious particles after infection with pathogenic agents was tested as a model for screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune activation. Two types of interventions were assessed: use of either the immunosuppressive drug prednisolone or an HIV-1 envelope-targeted toxin (sCD4-PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by splenocytes in vitro and, when administered to transgenic mice, suppressed the induction of plasma p24, as well as the ex vivo production of p24 and infectious virus stimulated by in vivo infection with Mycobacterium avium. Moreover, HIV-1 mRNA levels in the spleen were greatly reduced in mice treated with either agent. Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice, this model may be of particular advantage for testing interventions that target virus production by non-T cell virus reservoirs.
Schito
M L
ML
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. mschito@niaid.nih.gov
Kennedy
P E
PE
Kowal
R P
RP
Berger
E A
EA
Sher
A
A
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015704:CD4 Antigens / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000008:administration & dosage / Q000494:pharmacology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides; D051379:Mice; D008822:Mice, Transgenic; D009162:Mycobacterium avium; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D011533:Proviruses / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000821:virology
D019380:Anti-HIV Agents; D015704:CD4 Antigens; C057689:CD4-Pseudomonas toxin; D005098:Exotoxins; D005938:Glucocorticoids; D016655:HIV Core Protein p24; D000922:Immunotoxins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D011239:Prednisolone