We used our humanized mouse model to investigate the therapeutic effects of interferon alpha subtype 14 against HIV infection in vivo. We previously showed that human IFN-alpha14 subtype had potent anti-HIV activity, and was much stronger than the IFN-alpha2 subtype, which is currently in HIV-1 clinical trials. We used our TKO_BLT-humanized mouse model to test the efficacy of IFN-alpha14 in treatment of latent HIV infections when combined with oral combination antiretroviral therapy. The animal experiments have been completed and a manuscript describing the results has been submitted. The combination of antiretroviral drugs and IFNa14 reduced virus loads but did not cure the infections.. It is important to understand how the latent reservoir of HIV-1 becomes established because it is the latent virus that becomes reactivated if antiretroviral therapy is interrupted. In collaboration with Warner Greene at the Gladstone Institute we have completed animal experiments to determine if CCR2+/CCR5+ CD4+ T cells are the main reservoirs of virus. Samples from the animals are being evaluated for HIV-1 RNA and DNA levels by our collaborator, Ulf Dittmer. Experiment testing the efficacy of anti-CD47 immunotherapy in HIV-1-infected humanized mice produced evidence that anti-CD47 could reduce HIV-1 virus loads in established infections. We are unable to follow up on these results, replicate them and determine the mechanisms of action of anti-CD47 because of the Executive Order banning intramural scientists from using fetal tissue in research. A manuscript containing the preliminary results has been submitted.

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Lavender, Kerry J; Williamson, Brandi N; Saturday, Greg et al. (2018) Pathogenicity of Ebola and Marburg Viruses Is Associated With Differential Activation of the Myeloid Compartment in Humanized Triple Knockout-Bone Marrow, Liver, and Thymus Mice. J Infect Dis :
Hasenkrug, Kim J; Chougnet, Claire A; Dittmer, Ulf (2018) Regulatory T cells in retroviral infections. PLoS Pathog 14:e1006776
Lavender, Kerry J; Pace, Craig; Sutter, Kathrin et al. (2018) An advanced BLT-humanized mouse model for extended HIV-1 cure studies. AIDS 32:1-10
Van Dis, Erik S; Moore, Tyler C; Lavender, Kerry J et al. (2016) No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts. Virology 488:88-95
Lavender, Kerry J; Gibbert, Kathrin; Peterson, Karin E et al. (2016) Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol 90:6001-6013
Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B et al. (2016) Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID ""Meet the Experts"" 2015 Workshop Summary. AIDS Res Hum Retroviruses 32:109-19
Harper, Michael S; Guo, Kejun; Gibbert, Kathrin et al. (2015) Interferon-? Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS Pathog 11:e1005254
Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J et al. (2013) BLT-humanized C57BL/6 Rag2-/-?c-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood 122:4013-20