A cellular protein that helps guide immune cells to the gut has been newly identified as a target of HIV when the virus begins its assault on the body's immune system, according to researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
"The identification of this new receptor opens up new avenues of investigation that may help further elucidate the complex mechanisms of the pathogenesis of HIV infection" says NIAID director Anthony S. Fauci, MD, chief of the Institute's Laboratory of Immunoregulation (LIR) and senior author of the new study.
Several other immune cell receptors bind to HIV. Most important among these, the CD4 molecule, identified as an HIV receptor in 1984, functions as the principal receptor for HIV. The CCR5 and CXCR4 molecules, discovered in 1996, serve as co-receptors that HIV uses to enter its target cells. In the new study, which appears online Feb. 10, 2008 in Nature Immunology, NIAID scientists identify a cell adhesion molecule known as integrin alpha 4 beta 7 as another potentially important receptor for HIV.
Early in the course of HIV infection, the virus rapidly invades and replicates in gut-associated lymphoid tissue (GALT), the immune cells of the gut. Once seeded with HIV, the gut is rapidly depleted of CD4+ T cells, the main target of HIV, triggering the process that ultimately leads to AIDS.
"In the very early days of infection, it is in the GALT where most of the damage caused by HIV occurs," says Elena Martinelli, PhD, a lead author of the paper and a fellow in Fauci's laboratory. "The gut is where the virus really takes hold. We found that integrin alpha 4 beta 7, whose natural function is to direct T cells to the GALT, is also a receptor for HIV. It is very unlikely that this is a coincidence."
Martinelli, along with Claudia Cicala, PhD, James Arthos, PhD, and their colleagues found that the gp120 protein, part of the HIV envelope, binds to integrin alpha 4 beta 7 on CD4+ T cells, which promotes the formation of a stable junction, or synapse, between neighboring cells.
"A synapse is a junction that allows two cells to adhere in a stable way," says Arthos. "Many viruses have found a way to trick cells into forming these stable junctions. Now it appears that HIV can also trigger synapse formation."
Specifically, a short piece of the HIV gp120 protein in a region known as the V2 loop recognizes the alpha 4 chain of the integrin molecule on host cells. This stretch of the V2 loop is similar to part of the naturally occurring molecules that bind integrin alpha 4 beta 7. Thus, it appears that HIV is mimicking the natural molecular partners, or ligands, that normally bind to the receptor. The authors note, however, that some HIV isolates react more strongly to integrin alpha 4 beta 7 than others.
"The ability of a particular virus to bind to integrin alpha 4 beta 7 may determine whether it will have a major impact in targeting the gut lymphoid tissue," says Fauci. "This finding could be a significant determinant in the pathogenic mechanisms that lead to AIDS."
As part of the natural homing process, integrin alpha 4 beta 7 binds to its natural ligands and activates a protein known as LFA-1. According to Arthos, HIV can co-opt this process by mimicking the cells' alpha 4 beta 7 receptor natural ligands. When HIV gp120 protein binds to the alpha 4 beta 7 receptor it facilitates the formation of a synapse. Thus, HIV tricks an infected cell into binding to an uninfected cell, enabling HIV to readily gain access to the uninfected cell.
"While this study provides important new information concerning the various mechanisms by which HIV debilitates the human immune system, it also raises new questions and challenges that our laboratory and others will pursue," notes Cicala.
Reference: Arthos J et al. HIV-1 envelope protein binds to and signals through integrin alpha 4 beta 7, the gut mucosal homing receptor for peripheral T cells. Nature Immunology DOI: 10.1038/ni1566 (2008).
Source: National Institutes of Health
Â
Stay prepared and protected with Infection Control Today's newsletter, delivering essential updates, best practices, and expert insights for infection preventionists.
Reducing Hidden Risks: Why Sharps Injuries Still Go Unreported
July 18th 2025Despite being a well-known occupational hazard, sharps injuries continue to occur in health care facilities and are often underreported, underestimated, and inadequately addressed. A recent interview with sharps safety advocate Amanda Heitman, BSN, RN, CNOR, a perioperative educational consultant, reveals why change is overdue and what new tools and guidance can help.
New Study Explores Oral Vancomycin to Prevent C difficile Recurrence, But Questions Remain
July 17th 2025A new clinical trial explores the use of low-dose oral vancomycin to prevent Clostridioides difficile recurrence in high-risk patients taking antibiotics. While the data suggest a possible benefit, the findings stop short of statistical significance and raise red flags about vancomycin-resistant Enterococcus (VRE), underscoring the delicate balance between prevention and antimicrobial stewardship.
What Lies Beneath: Why Borescopes Are Essential for Verifying Surgical Instrument Cleanliness
July 16th 2025Despite their smooth, polished exteriors, surgical instruments often harbor dangerous contaminants deep inside their lumens. At the HSPA25 and APIC25 conferences, Cori L. Ofstead, MSPH, and her colleagues revealed why borescopes are an indispensable tool for sterile processing teams, offering the only reliable way to verify internal cleanliness and improve sterile processing effectiveness to prevent patient harm.
The Next Frontier in Infection Control: AI-Driven Operating Rooms
Published: July 15th 2025 | Updated: July 15th 2025Discover how AI-powered sensors, smart surveillance, and advanced analytics are revolutionizing infection prevention in the OR. Herman DeBoard, PhD, discusses how these technologies safeguard sterile fields, reduce SSIs, and help hospitals balance operational efficiency with patient safety.
Targeting Uncertainty: Why Pregnancy May Be the Best Time to Build Vaccine Confidence
July 15th 2025New national survey data reveal high uncertainty among pregnant individuals—especially first-time parents—about vaccinating their future children, underscoring the value of proactive engagement to strengthen infection prevention.