NDLI: Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus

Content Provider	PubMed Central
Author	Hadas, Eran Chao, Wei He, Hongxia Saini, Manisha Daley, Eleen Saifuddin, Md Galina, Bentsman Ganz, Eric Volsky, David J. Potash, Mary Jane
Copyright Year	2013
Abstract	Heterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV) cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1–7 nights. At 1–6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR) amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70–100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2′,3′-dideoxcytidine (ddC) or tenofovir largely prevented their EcoHIV/NDK infection by mating (P<0.05 and P<0.003, respectively). In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003) but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.
Related Links	http://dx.doi.org/10.1242/dmm.012617
Ending Page	1298
Page Count	7
Starting Page	1292
File Format	PDF
ISSN	17548403
e-ISSN	17548411
Journal	Disease Models & Mechanisms
Issue Number	5
Volume Number	6
Language	English
Publisher	The Company of Biologists Limited
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	The Company of Biologists Limited
Subject Keyword	Immunology and Microbiology (miscellaneous) Biochemistry, Genetics and Molecular Biology(all) Medicine (miscellaneous) Neuroscience (miscellaneous) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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Remarks on the article of Hadas et al.: Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus

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