HIV-1 infection of monocyte-derived macrophages reduces Fc and complement receptor expression

Kent, Stephen J.; Stent, Gianna; Sonza, Secondo; Hunter, S D; Crowe, Suzanne

doi:10.1111/j.1365-2249.1994.tb07017.x

Cited by 27 publications

(6 citation statements)

References 45 publications

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“…Petit et al 43 reported increased CD11b expression on HIV-1-infected U937 cells, while CD11b was found to be either increased 44 or unaltered 45 on monocytes from HIV-1-infected subjects, and decreased on HIV-1-infected MDM 3 weeks postinfection in vitro. 46 At the time we measured phagocytosis by MDM 1 week postinfection, we showed that HIV-1 infection did not change the surface expression of CD11b or CD11c, or affect the binding of CЈ-opsonized targets to CЈRs. This indicates that the HIV-1-induced inhibition of phagocytosis occurs downstream of complement receptor binding.…”

Section: Prior To Reverse Transcriptionmentioning

confidence: 87%

Impaired Complement-Mediated Phagocytosis by HIV Type-1-Infected Human Monocyte-Derived Macrophages Involves a cAMP-Dependent Mechanism

Azzam

Kedzierska

Leeansyah

et al. 2006

AIDS Research and Human Retroviruses

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HIV-1 infection of cells of macrophage lineage impairs a number of effector functions performed by these cells, including phagocytosis of opsonized pathogens. In this study we investigate the effects of HIV-1 on the mechanism of complement (C')-mediated phagocytosis by human monocyte-derived macrophages (MDM). Using C'-opsonized sheep red blood cells (sRBC) as targets, we demonstrate that phagocytosis is inhibited by HIV-1 infection in vitro. Inhibition is not due to downregulation of surface C' receptors (R) or altered binding of C'-opsonized targets to HIV-1-infected MDM, suggesting a postreceptor-mediated mechanism of suppression. Having shown that increased levels of intracellular cAMP in uninfected MDM inhibit phagocytosis, we demonstrate that HIV-1 infection of MDM is associated with increased intracellular cAMP. Using the adenylate cyclase inhibitors 2',5'-dideoxyadenosine and MDL-12,330A, we show that phagocytosis by HIV-1- infected MDM can be restored by inhibition of cAMP production. Defective phagocytosis by HIV-1-infected MDM did not correlate with prostaglandin secretion, and was less in uninfected MDM within the HIV-1-infected cell culture suggesting a minimal bystander effect. Inhibition required viral entry but not active viral replication, as shown by use of the antiretroviral drug lamivudine. Hence, our study suggests that HIV-1 impairs C'R-mediated phagocytosis in MDM by elevating intracellular cAMP levels, independent of prostaglandin secretion, and contributes to our understanding of how HIV-1 impairs cell-mediated immunity.

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Section: Prior To Reverse Transcriptionmentioning

confidence: 87%

Impaired Complement-Mediated Phagocytosis by HIV Type-1-Infected Human Monocyte-Derived Macrophages Involves a cAMP-Dependent Mechanism

Azzam

Kedzierska

Leeansyah

et al. 2006

AIDS Research and Human Retroviruses

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“…In this context, it should be noted that out of all the plasma-virus combinations tested in the current study, it was only in six cases that the antiviral effect of ADCMI was less than that of the neutralizing activity (Table 2). Furthermore, following infection and during the progression of HIV-1, declines in the expressions of CR1, CR2, and CR3 on immune cells have been noted (59,60), which may further diminish the CADE effect.…”

Section: Discussionmentioning

confidence: 99%

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Şahin

Holmgren

Sheik-Khalil

et al. 2013

J Virol

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Human immunodeficiency virus type 2 (HIV-2)-infected individuals develop immunodeficiency with a considerable delay andtransmit the virus at rates lower than HIV-1-infected persons. Conceivably, comparative studies on the immune responsiveness of HIV-1-and HIV-2-infected hosts may help to explain the differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than in HIV-1 infection. In the present study, we have examined further the function of the humoral immune response and studied the effect of complement on the antiviral activity of plasma from singly HIV-1-or HIV-2-infected individuals, as well as HIV-1/ HIV-2 dually infected individuals. The neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4.CCR5 cells. The results showed that the addition of complement increased intratype antiviral activities of both HIV-1 and HIV-2 plasma samples, although the complement effect was more pronounced with HIV-2 than HIV-1 plasma. Using an area-under-the-curve (AUC)-based readout, multivariate statistical analysis confirmed that the type of HIV infection was independently associated with the magnitude of the complement effect. The analyses carried out with purified IgG indicated that the complement effect was largely exerted through the classical complement pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates the efficient use of complement and thereby may be one factor contributing to a strong antiviral activity present in HIV-2 infection.

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“…These cells strongly express FcgRI, and, to a lesser extent, FcgRII and FcgRIII. 22 A strong binding was observed without significant differences between Abs (see Supplementary Figure S1 online). As expected, the binding of b12 to macrophages was Fc mediated, as the LALA mutant was not able to bind these cells.…”

Section: Binding Of Anti-hiv Mabs To Hiv and Fccrsmentioning

confidence: 98%

Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques

et al. 2014

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Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcγ receptor (FcγR)-mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FcγR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.

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HIV-1 infection of monocyte-derived macrophages reduces Fc and complement receptor expression

Cited by 27 publications

References 45 publications

Impaired Complement-Mediated Phagocytosis by HIV Type-1-Infected Human Monocyte-Derived Macrophages Involves a cAMP-Dependent Mechanism

Impaired Complement-Mediated Phagocytosis by HIV Type-1-Infected Human Monocyte-Derived Macrophages Involves a cAMP-Dependent Mechanism

Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent

Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques

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