Clinical Significance of Neutrophil Functional Activity in HIV Infection

As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins. Most proteins that become altered by this system do not belong to the invading microorganism but to the host. While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action. We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1. HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI). Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant. The unmodified plasma protein fraction had no effect. HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation. These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells. Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms.

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“…In addition to neutropenia, a variety of qualitative defects in neutrophil function has been described in HIV-1 infection [48]–[50].…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Turn Plasma Proteins into Weapons against HIV-1

et al. 2013

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“…In addition, coinfection worsens neutrophilic impairment (36). Toxoplasma gondii is often responsible for disseminated reactivations in AIDS patients, especially in neurotoxoplasmosis (70).…”

Section: Intracellular Microorganism Phagocytosis and Hiv Infectionmentioning

confidence: 99%

Phagocytic Activity in Human Immunodeficiency Virus Type 1 Infection

Pugliese

Vidotto

Beltramo

et al. 2005

Clin Vaccine Immunol

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“…Studies have indicated that an increased susceptibility of HIV infected subjects to bacterial infections may be due to phagocyte dysfunction [7,9]. It has been suggested that qualitative defects in the phagocytic function in HIV infection can impair chemotaxis, alter phagocytosis, lower oxidative burst capacity and alter bacterial killing [10,11]. The enzymes that are involved in the phagocytic process may be modulated in HIV infection.…”

mentioning

confidence: 99%