Investigating novel HIV reservoirs in the pulmonary vasculature

Active Project Grant Awarded Last action

Award ID
R21AI181657
Recipient
Awarding agency
Obligated
$584,293

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 76% complete
Originally
Place of performance
Lubbock, TX 79430, USA

Award details come from USAspending.gov.

Description

Abstract
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.

Transactions

Action Obligated Date
Amendment $0
Amendment $0
Amendment $189,570
Amendment $189,570
Original award $205,153

Quick answers

Who received award R21AI181657?

R21AI181657 was awarded to Texas TECH University Health Sciences Center by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 12, 2024.

How much is award R21AI181657 worth?

$584,293 has been obligated on R21AI181657.

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