Selected Grantee Publications
CD8+ Lymphocytes Do Not Impact SIV Reservoir Establishment under ART
Statzu et al., Nature Microbiology. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894752/
The HIV-1 latent reservoir has been shown to persist following antiretroviral therapy (ART), but the mechanisms underlying the establishment and maintenance of the reservoir are not fully understood. Using rhesus macaques of both sexes, investigators examined the effects of CD8+ T cells on formation of the latent reservoir with simian immunodeficiency virus (SIV) infection. They found that CD8+ T cell depletion resulted in slower decline of viremia but did not change the frequency of infected CD4+ T cells in the blood or lymph nodes. Additionally, the size of the persistent reservoir was unchanged. These findings suggest that the viral reservoir is established largely independent of SIV-specific cytotoxic T lymphocyte control. Supported by ORIP (P51OD011132), NIAID, NCI, NIDDK, NIDA, NHLBI, and NINDS.
Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection
Abeynaike et al., Viruses. 2023.
https://www.mdpi.com/1999-4915/15/2/365
A major obstacle to human natural killer (NK) cell reconstitution is the lack of human interleukin‑15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor. Researchers show that immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice expressing a transgene encoding human IL-15 (NSG-Tg(IL-15)) have physiological levels of human IL-15 and support long-term engraftment of human NK cells when transplanted with human umbilical cord blood–derived hematopoietic stem cells (HSCs). These mice demonstrate robust and long-term reconstitution with human immune cells but do not develop graft-versus-host disease, allowing long-term studies of human NK cells. The HSC-engrafted mice can sustain HIV-1 infection, resulting in human NK cell responses. This work provides a robust novel model to study NK cell responses to HIV-1. Supported by ORIP (R24OD026440), NIAID, NCI, and NIDDK.
Surrogate Biomarkers of Disease Progression in Human Pegivirus Seropositive Human Immunodeficiency Virus–Infected Individuals
Vimali et al., Viral Immunology. 2023.
Researchers have previously observed that human pegivirus (HPgV) infection is associated with reduced progression of HIV. Investigators examined markers of HIV progression in male and female individuals with HIV and HPgV infection. They reported that HIV plasma viral load was lower in HPgV-seropositive individuals with HIV than in HPgV‑seronegative individuals with HIV. They also found that clinical markers of hepatic damage were significantly lower in HPgV-seropositive individuals with HIV. Future work could examine pathways through which HPgV influences HIV control, which might inform the development of new therapeutics. Supported by ORIP (P51OD011132) and NIAID.
Duration of Antiretroviral Therapy Impacts the Degree of Residual SIV Infection in the Gut in Long‐Term Non‐Progressing Chinese Rhesus Macaques
Solis-Leal et al., Journal of Medical Virology. 2023.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.28185
HIV and simian immunodeficiency virus (SIV) reservoirs have been shown to persist with antiretroviral therapy (ART), particularly in the gut‐associated lymphoid tissues in the intestine. The effects of ART on the reservoir size, however, had not been explored fully. In this study, researchers used male Chinese‐origin rhesus macaques to assess the effects of long- and short-term ART on gut infection—across segments of the small and large intestines—in long‐term non‐progressors (LTNPs). They reported that although ART does not eliminate SIV in LTNPs, a longer ART period dramatically reduces SIV infection and diversity in the gut. Further studies are needed to better understand the reduction of HIV gut reservoirs in this context. Supported by ORIP (P51OD011133, P51OD011104), NIAID, NIMH, and NINDS.