HIV-1 Pathogenesis and Immunity

A large part of my career has been spent advancing our understanding of HIV-1 transmission, immune evasion, antibody responses, and small molecule therapeutics. To date, my research has provided critical insights into viral spread mechanisms, innate immune modulation, antibody functions, and drug efficacy, informing novel therapeutic and vaccine development strategies.


Key Areas of Focus:

Innate Immunity in HIV-1: During my Ph.D., I identified and characterized WFDC1, an innate immune effector molecule that enhances HIV-1 infection by promoting intercellular adhesive junctions, facilitating cell-to-cell viral transfer.

Mechanisms of Immune Evasion: My work has also focused on how HIV-1 evades immune responses, particularly through Vpu-mediated suppression of antibody-dependent cellular cytotoxicity (ADCC), with his findings featured in Nature Reviews Microbiology.

HIV-1 Cell-Cell Transmission: My research on virological synapses revealed how HIV spreads directly between T cells, evading neutralizing antibodies and promoting efficient transmission.

FcR-Mediated Antibody Functions in HIV Control: My research characterized the roles of non-neutralizing antibodies and Fc receptor (FcR) signaling, showing how these responses contribute to HIV control. Additionally, my work detailed how Vpu antagonizes FcR-mediated responses, including ADCC.

Small Molecule Drug Effects on HIV Replication: My work has also evaluated the impact of small molecule inhibitors on HIV replication, including fostemsavir (temsavir) and P2X1 selective antagonists.


Selected Publications:

Weiss S, Alvarez R.A., et al. (2025). High HIV-1 viremia and delayed response to fostemsavir. Antiretroviral Research. (Co-first author)

Alvarez, R.A., et al. (2014). Vpu inhibition of ADCC. Journal of Virology. (Featured in Nature Reviews Microbiology)

Alvarez, R.A., et al. (2011). WFDC1 enhances cell-cell HIV transfer. Journal of Retrovirology.

Micsenyi, A.M., et al. (2013). Direct HIV-1 infection of cervical epithelial cells and T cell transmission. Journal of Infectious Diseases.

Alvarez, R.A., et al. (2014). HIV spread through T cell virological synapses. PLoS Pathogens.

Alvarez, R.A., Barría, M.I., et al. (2021). Endocytic motif modulation in HIV cell-to-cell transfer. Viruses. (Co-first author)

Soare, A.Y., et al. (2020). P2X1 antagonists block HIV-1 fusion. Journal of Virology.

Dale, B.M., Alvarez, R.A., et al. (2013). Small molecule effects on HIV spread. Immunological Reviews.

Alvarez, R.A., Maestre, A., et al. (2017). Fcγ receptor signaling in HIV controllers. JCI Insight. (Co-first/co-senior author)

Hioe, C.E., et al. (2022). Non-neutralizing antibodies reduce HIV burden in humanized mice. PLoS Pathogens. (Co-senior author)

Zolla-Pazner, S., et al. (2019). V1V2-specific antibodies and vaccine protection. Current Opinion in HIV/AIDS.

My research continues to drive advancements in HIV-1 pathogenesis, immune modulation, antibody function, and drug development, informing strategies for novel therapeutic interventions and vaccine design.