Testing antiretroviral drug efficacy in conventional mice infected with chimeric HIV-1

Eran Hadas, Alejandra Borjabad, Wei Chao, Manisha Saini, Kozi Ichiyama, Mary Jane Potash, David J. Volsky

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

OBJECTIVE: We previously described chimeric HIV-1, EcoHIV, which can infect mouse cells in culture and cause spreading infection in conventional immunocompetant mice. We have now applied this system as a model for preclinical evaluation of anti-retroviral drugs. DESIGN AND METHODS: We used chimeric virus EcoHIV/NDK constructed on the backbone of subtype D NDK. EcoHIV/NDK expression in mice was characterized 5-10 days after infection by testing viral DNA, RNA, and protein burdens in spleen and macrophages by real-time PCR (QPCR), RT-PCR, and p24 ELISA. For antiviral evaluation, groups of 5-7 mice were pretreated with 2′,3′-dideoxycytidine (ddC), abacavir, or vehicle; mice were then infected with EcoHIV/NDK, treatment maintained for additional 48 h, and tested for viral DNA and RNA burdens in spleens and macrophages by QPCR. RESULTS: EcoHIV/NDK infected mice reproducibly showed viral burdens of up to 1.4 × 10 viral DNA copies and 200 pg p24 per 10 spleen cells and expressed spliced Vif RNA and mature p24 in macrophages 5-10 days after infection. Treatment of mice with 60 or 300 mg ddC/kg/day blocked EcoHIV/NDK infection in a dose-dependent manner with significantly lower viral DNA and RNA burdens at both drug doses (P < 0.001) in the spleens of infected mice. Abacavir tested at 100 mg/kg/day caused 96% inhibition of viral DNA synthesis in spleen and it almost completely abolished viral spliced RNA synthesis in spleens and macrophages. CONCLUSIONS: The system of chimeric HIV-1 infection of mice permits rapid, statistically powerful, and inexpensive evaluation of antiretroviral drugs in vivo.

Original languageEnglish
Pages (from-to)905-909
Number of pages5
JournalAIDS
Volume21
Issue number8
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Abacavir
  • Animal models of HIV/AIDS
  • Anti-HIV drug testing in mice
  • Antiretroviral drugs
  • Chimeric HIV
  • Drug efficacy in vivo
  • HIV infection of mice
  • HIV-1
  • Real-time PCR
  • Virus burden in mice
  • ddC

Fingerprint

Dive into the research topics of 'Testing antiretroviral drug efficacy in conventional mice infected with chimeric HIV-1'. Together they form a unique fingerprint.

Cite this