Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV

Abstract

Nerve growth factor (NGF) is a neurotrophin with the ability to exert specific effects on cells of the immune system. Human monocytes͞macrophages (M͞M) infected in vitro with HIV type 1 (HIV-1) are able to produce substantial levels of NGF that are associated with enhanced expression of the high-affinity NGF receptor (p140 trkA) on the M͞M surface. Treatment of HIVinfected human M͞M with anti-NGF Ab blocking the biological activity of NGF leads to a marked decrease of the expression of p140 trkA high-affinity receptor, a concomitant increased expression of p75 NTR low-affinity receptor for NGF, and the occurrence of apoptotic death of M͞M. Taken together, these findings suggest a role for NGF as an autocrine survival factor that rescues human M͞M from the cytopathic effect caused by HIV infection.

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

“…The doses of RAL and other INIs able to inhibit the HIV-1 in M/M were lower compared to those for PBMCs and T cells (Table 1), although these differences were without statistical significance. This biological effect could be correlated to the peculiar characteristics of HIV-1 replication in M/M, which is quite different from that observed in CD4+ T lymphocytes (Aquaro et al, 2002a,b;Badley et al, 1997;Bagnarelli et al, 1996;Garaci et al, 1999;Gendelman et al, 1986;Michelini et al, 2010;Orenstein et al, 1988). Indeed, M/M are resting, terminally differentiated cells that undergo replication only under very peculiar conditions and situations; this makes the whole integration phenomenon more difficult, as it occurs during the replication cycle of cells (Kelly et al, 2008).…”

Macrophages and HIV-1: dangerous liaisons

“…The relationships between AMM and the neurotrophin family may also be critical for the establishment and long-term persistence of the virus reservoir in the brain. Indeed, HIV infection per se induces NGF expression in macrophages (Garaci et al, 1999), leading to an autocrine loop involving NGF and its high affinity receptor TrkA for macrophage survival despite massive virus production. This survival effect involves bcl2, bcl-xL and bfl1 anti-apoptotic molecules (la Sala et al, 2000) and is abrogated by NGF neutralisation leading to p75NTR-mediated apoptosis (Caroleo et al, 2001;Garaci et al, 1999).…”

“…Indeed, HIV infection per se induces NGF expression in macrophages (Garaci et al, 1999), leading to an autocrine loop involving NGF and its high affinity receptor TrkA for macrophage survival despite massive virus production. This survival effect involves bcl2, bcl-xL and bfl1 anti-apoptotic molecules (la Sala et al, 2000) and is abrogated by NGF neutralisation leading to p75NTR-mediated apoptosis (Caroleo et al, 2001;Garaci et al, 1999). This could be a powerful mechanism for maintaining viral replication (Garaci et al, 2003), especially in the restrictive CNS milieu, and illustrates exactly how HIV uses endogenous molecules for its own benefit.…”

Nanoparticles increase human bronchial epithelial cell susceptibility to respiratory syncytial virus infection via nerve growth factor-induced autophagy

“…In previous work, we had demonstrated that this same pattern of neurotrophins expression prevents the apoptotic death of RSV‐infected airway epithelial cells, thereby enhancing epithelial viability with a mechanism similar to that previously described in macrophages infected with human immunodeficiency virus (HIV) and essential for the host cell to survive while supporting the production of new viral particles (Garaci et al. 1999). …”