Complement, Fc receptors and antibodies: a Trojan horse in HIV infection?

Stoiber, Heribert

doi:10.1097/coh.0b013e32832f0108

Cited by 11 publications

(6 citation statements)

References 86 publications

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“…Immune-enhancement has been observed for HIV and influenza infection [28], [29], yet an impact on the clinical outcome is known particularly for dengue disease. An infection-enhancing role for non-neutralizing antibodies has been suggested based on in vitro infection of the K562 cell line or primary monocytes in the presence of serum or monoclonal antibodies [30], [31].…”

Section: Discussionmentioning

confidence: 99%

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

et al. 2011

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BackgroundDengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection.Methodology/Principal FindingsWe assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4–7 days after fever onset was more than 50% even after primary infection.Conclusions/SignificancePoly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and “innate specificities” seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development.

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Section: Discussionmentioning

confidence: 99%

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

et al. 2011

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“…41 Moreover, recent data have indicated that complement activation may rather enhance HIV infection at later stages through the binding of HIV-complement immune complexes to complement receptor positive cells. 42 Serum IgA also contributes to the control of HIV replication by triggering antibody-dependent cellular cytotoxicity (ADCC) through myeloid IgA receptor Fc␣RI. 43 The involvement of IgG and Fc␥R-mediated ADCC to mucosal protection of HIV infection appears to be more complicated.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice

Hur

Patel

Shimizu

et al. 2012

Blood

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“…Thus, the role of the complement system in HIV-1 infection appears to be multifaceted and seems to be dependent on the presence of complement regulatory proteins (CRPs) in the HIV-1 envelope and on the presence of complement receptors (CRs) on the surfaces of target cells. Virus inactivation through opsonization and lysis has been reported to dominate when the expression of CRPs on the HIV-1 envelope is limited, whereas the presence of CRs on the target cells may enhance viral infectivity (21)(22)(23). With just two exceptions (24,25), it should be noted that little is known on the role of complement in HIV-2 infection.…”

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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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Complement, Fc receptors and antibodies: a Trojan horse in HIV infection?

Abstract: This review highlights current knowledge in this field and emphasizes the contribution of complement and non-neutralizing antibodies in controlling versus and enhancing infection.

Cited by 11 publications

References 86 publications

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

Dengue Virus Activates Polyreactive, Natural IgG B Cells after Primary and Secondary Infection

Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice

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

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