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Investigating Novel HIV Reservoirs in the Pulmonary Vasculature

Award Number: R21AI181657
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Investigating Novel HIV Reservoirs in the Pulmonary Vasculature - PROJECT SUMMARY Infections with Human Immunodeficiency Virus (HIV) remain a major global public health concern. The HIV reservoirs are a leading reason for which HIV infection remains without a cure. HIV integrates its viral DNA into the host cell DNA. Cell activation leads to transcription of archived viral information, which can refuel viral replication even in the presence of antiretroviral therapy (ART). This may be problematic when cellular reservoirs of HIV involve cell types that are in continuous functional activation. Research conducted by others and us have shown that pvSMC are susceptible to HIV infection. In addition, people living with HIV (PLWH) are more prone to comorbidities that involve chronic vascular constriction. Our preliminary studies suggest that pulmonary arterial smooth muscle cells are susceptible to HIV infection, sustain the infection during ART-induced viral suppression, and are capable to release infectious viruses that can infect bystander T cells. Our preliminary findings have significant importance because identifying and eliminating HIV reservoirs such as pvSMC is critical to the success of global efforts to cure HIV. The fact that PLWH are more prone to pulmonary vasoconstrictive diseases implies that the persistent cell activation and vasoconstriction of pvSMC are likely to provide transcriptionally active HIV leading to reseeding of reservoirs. The pulmonary vasculature is heavily overlooked as an important source of HIV, leading to a significant gap in the literature about non-immune cell sources such as pvSMC as HIV reservoirs. Herein, we propose to determine the ability of pvSMC to support chronic HIV infection and their ability to spread HIV to bystander immune cells in the presence of ART. We also propose to investigate the cellular mechanisms for the resiliency of pvSMC to the cytopathic effects of HIV. This work should provide new insights into the potential of pulmonary vascular as SMC as reservoirs in the era of advanced ART. Knowing the characteristics of pvSMC as HIV reservoirs is imperative to further strategize for the effective eradication of a previously unappreciated HIV reservoir.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $189,570 )
2025	2025	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST	LUBBOCK	TX	79430	LUBBOCK	USA	Allergy and Infectious Diseases Research	000	2	7/8/2025	NON-COMPETING CONTINUATION	$189,570
														Subtotal = $189,570

Issue Date FY: 2024 ( Subtotal = $205,153 )
2024	2024	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST	LUBBOCK	TX	79430	LUBBOCK	USA	Allergy and Infectious Diseases Research	000	1	8/12/2024	NEW	$205,153
														Subtotal = $205,153

Grand Total All Awards = $394,723

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Investigating Novel HIV Reservoirs in the Pulmonary Vasculature

Award Number: R21AI181657

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/12/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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