In FY 2016 we used our humanized mouse model to investigate HIV in several ways. Most importantly, experiments in FY2016 revealed that our TKO-BLT humanized mouse model can be used in long-term studies (up to one year) with ART administered by injections or via an oral route (drugs incorporated into mouse chow). Such mice develop chronic and latent HIV infections. We have demonstrated that HIV viral loads in these mice can be suppressed to levels undetectable by highly sensitive PCR tests for viremia and provirus. Importantly, the mice are extremely sensitive tools for cure studies as mice with undetectable virus relapse with high viremia following withdrawal of ART. The goal of the upcoming year will be to test HIV Cure drugs using this model. Two published studies in 2016 also demonstrated that human alpha interferon subset 14 works much better in vitro and in vivo to suppress HIV than subset 2, which is currently in clinical trials. Further studies combining IFNa14 with ART are underway. Using our humanized mouse model, we also investigated the role of amyloid fibrils from semen-derived peptide (SEVI) in enhancing HIV-1 infectivity in vivo. We confirmed that SEVI enhanced infectivity in vitro but found no enhancement via the rectal route in vivo. These studies bring into question the utility of using SEVI inhibitors as prophylactics.

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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