The Role of Defensins in HIV Pathogenesis

Abstract

Profound loss of CD4+ T cells, progressive impairment of the immune system, inflammation, and sustained immune activation are the characteristics of human immunodeficiency virus-1 (HIV-1) infection. Innate immune responses respond immediately from the day of HIV infection, and a thorough understanding of the interaction between several innate immune cells and HIV-1 is essential to determine to what extent those cells play a crucial role in controlling HIV-1 in vivo. Defensins, divided into the three subfamilies α-, β-, and θ-defensins based on structure and disulfide linkages, comprise a critical component of the innate immune response and exhibit anti-HIV-1 activities and immunomodulatory capabilities. In humans, only α- and β-defensins are expressed in various tissues and have broad impacts on HIV-1 transmission, replication, and disease progression. θ-defensins have been identified as functional peptides in Old World monkeys, but not in humans. Instead, θ-defensins exist only as pseudogenes in humans, chimpanzees, and gorillas. The use of the synthetic θ-defensin peptide “retrocyclin” as an antiviral therapy was shown to be promising, and further research into the development of defensin-based HIV-1 therapeutics is needed. This review focuses on the role of defensins in HIV-1 pathogenesis and highlights future research efforts that warrant investigation.

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy

“…Recombinant hBD-2 (and hBD-3) was shown to inactivate HIV-1 in vitro directly. Contrarily, elevated hBD-2 levels in connection with microbial translocation in the gastrointestinal (GI) tract in HIV-infected individuals or genital infections in HIV-infected women may also promote local inflammation and viral transmission [22]. Levels of hBD-2 were, however, lower in our cohort of PLHIV compared to HC, which might indicate reduced anti-HIV-1 activity of defensins in long-term treated HIV-infected patients.…”

Antimicrobial activity, mechanism of action, and methods for stabilisation of defensins as new therapeutic agents

“…Antimicrobial activity of hBD-3 has also been reported against multidrug resistant clinical isolates of S. aureus, Enterococcus faecium, and P. aeruginosa, as well as against Stenotrophomonas maltophilia and Acinetobacter baumannii [34]. For b-defensins, anti-HIV activity is reported only for hBD-2 and hBD-3, which block the virus's replication [35,36].…”

Downregulation of Defensin genes in SARS-CoV-2 infection

“…Antiviral activity of defensins against HIV and other viruses suggest that defensins have a role in host-defense not only against bacteria. Their expression in several cell types and tissues [22] suggest that they can act as the first line of defense against viruses targeting various cell types. HD-5 has been shown to inhibit SARS-CoV-2 in vitro by binding to Angiotensin-converting enzyme-2 (ACE2), the cellular receptor for the virus [24].…”