Pair of NIH grants provide $5.5 million for HIV research
An estimated 27,000 people with HIV live in Virginia — including about 8,000 in Hampton Roads.
Dr. Woong-Ki Kim and Dr. Ming Lei Guo hope their research will help improve these patients’ lives.
Simian Immunodeficiency Virus infected macrophages (green)surround a blood vessel (red) with cell nuclei (blue) in the brain of an infected Rhesus macaque.
People who are HIV positive can expect to live an average lifespan — a prospect unheard of only a generation ago.
But while anti-retroviral drugs have tamed a key aspect of this once-deadly condition, HIV has proven to be a stubborn adversary that continues to linger and haunt its victims. Two EVMS faculty members hope to help ease this burden. Woong-Ki Kim, PhD, and Ming-Lei Guo, PhD, received a pair of R01 grants totaling $5.5 million from the National Institutes of Health to fund research to better understand the virus. NIH R01 grants are among the most sought-after, prestigious grants awarded for medically oriented research.
Dr. Kim, Associate Dean for Research Faculty Development and Research Facilities and Professor of Microbiology and Molecular Cell Biology, is continuing his work to find and eliminate remnants of the virus that persist even after treatment.
"Despite effective anti-retroviral therapy (ART) that maintains HIV at non-detectable levels [in blood], HIV is not eradicated," Dr. Kim says.
"When individuals are off ART, or during ‘viral blips,’ viral reservoirs in the central nervous system can quickly rebound."
Dr. Kim and others have found that a favorite hiding place is in perivascular macrophages (PVMs) — a type of protective white blood cell found in the central nervous system. Despite ART treatment, this HIV reservoir persists, silently awaiting an opportunity to attack the body once again.
HIV targets these macrophages early during infection and throughout infection even with effective ART, Dr. Kim says.
In his research, funded by a $3.6 million grant, Dr. Kim is using an experimental anti-cancer compound to try to prevent the virus from accumulating in the brain. He will test at multiple intervals — three and five months — to make sure the process is successful. If it works in animal models, it could eventually make its way into human research.
Simian Immunodeficiency Virus infected macrophages (green)surround a blood vessel (red) with cell nuclei (blue) in the brain of an infected Rhesus macaque.
Dr. Guo, Assistant Professor of Pathology and Anatomy, is the first faculty recruit through the new Center for Integrative Neuroscience and Inflammatory Diseases (CINID). He is working with Dr. Kim, also a member of the CINID team, on a second HIV-related grant, valued at $1.9 million to study the impact of HIV on neuropsychiatric disorders.
"People living with HIV have comparable life-expectancy as their HIV-negative peers, but their life-quality is deeply compromised due to the high prevalence of neuropsychiatric disorders, including depression and anxiety," Dr. Guo says. No effective treatment exists.
Among people with HIV, drug abuse is very common, particularly in developed countries, says Dr. Guo, who has had three previous NIH grants focused on HIV and drug abuse. Evidence suggests there are several potential contributing factors, including proteins expressed by the concealed virus and antiretrovirals used long term to suppress the virus, as well as the impact of cocaine and other drugs of abuse.
Drs. Guo and Kim are focused on a newly identified pathway known as “NLRP3 inflammasome signaling.” Tantalizing preliminary data points to NLRP3 as a key part of the intracellular communications behind the neurological damage, Dr. Guo says. They will test this hypothesis and determine if blocking these communications prevents neurological damages.
Their research findings could provide a foundation for the development of treatments to help ease the disorders and perhaps even reverse the neuronal damage. Potentially, a medication to block NLRP3 could be used to prevent the damage, Dr. Guo says.
Read more magazine stories from issue 14.2 or read stories from past issues.
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