HIV and HIV-infected cells differentially activate the human complement system independent of antibody

Sölder, B; Schulz, Thomas F.; Hengster, Paul; Löwer, Johannes; Larcher, Clara; Bitterlich, G.; Kurth, Reinhard; Wächter, Helmut; Dierich, Manfred P.

doi:10.1016/0165-2478(89)90180-6

Cited by 77 publications

(28 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, depending on the cells producing HIV, the virus is more or less capable of activating complement. This might explain some of the reported discrepancies in studies measuring complement activation by HIV virions (34,(43)(44)(45)(46). The data we have obtained indicate that the viruses produced by the Hut/4 -3 cell line derived from human lymphocytes are complement activating even in the absence of specific Abs.…”

Section: Discussioncontrasting

confidence: 44%

Complement Mediates the Binding of HIV to Erythrocytes

Horáková

Gasser

Sadallah

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

A fraction of HIV is associated with erythrocytes even when the virus becomes undetectable in plasma under antiretroviral therapy. The aim of the present work was to further characterize this association in vitro. We developed an in vitro model to study the factors involved in the adherence of HIV-1 to erythrocytes. Radiolabeled HIV-1 (HIV) and preformed HIV-1/anti-HIV immune complexes (HIV-IC) were opsonized in various human sera, purified using sucrose density gradient ultracentrifugation, and incubated with human erythrocytes. We observed that, when opsonized in normal human serum, not only HIV-IC, but also HIV, bound to erythrocytes, although the adherence of HIV was lower than that of HIV-IC. The adherence was abolished when the complement system was blocked, but was maintained in hypogammaglobulinemic sera. Complement-deficient sera indicated that both pathways of complement were important for optimal adherence. No adherence was seen in C1q-deficient serum, and the adherence of HIV was reduced when the alternative pathway was blocked using anti-factor D Abs. The adherence could be inhibited by an mAb against complement receptor 1. At supraphysiological concentrations, purified C1q mediated the binding of a small fraction of HIV and HIV-IC to erythrocytes. In conclusion, HIV-IC bound to erythrocytes as other types of IC do when exposed to complement. Of particular interest was that HIV alone bound also to erythrocytes in a complement/complement receptor 1-dependent manner. Thus, erythrocytes may not only deliver HIV-IC to organs susceptible to infection, but free HIV as well. This may play a crucial role in the progression of the primary infection.

show abstract

Section: Discussioncontrasting

confidence: 44%

Complement Mediates the Binding of HIV to Erythrocytes

Horáková

Gasser

Sadallah

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Previous reports of "antibody-independent" C activation by HIV and HIV-infected cells were made by Solder et al [26] and Marschang et al [9]. These investigators observed that various laboratory isolates of HIV and.…”

Section: Discussionmentioning

confidence: 84%

“…Both groups further showed that C activation by HIV isolates occurred via the classical pathway, whereas C activation by HIV-infected cells occurred mainly through the alternative pathway. Initially, the proposed mechanism for C activation was the direct binding of gpl60 to C [26]. Subsequent studies, using a solid-phase binding assay, revealed that an external immunodominant region of gp41 was binding directly to the globular region of Clq.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of HIV-specific and ‘antibody-independent’ mechanisms for complement activation by HIV-infected cells

Saarloos¹,

Lint²,

Spear³

1995

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYPrevious studies in this laboratory have shown that efficient activation of complement (C) on HIV isolates and HIV-infected cells requires the binding of specific anii-HIV antibodies, while other investigators have observed "antibody-independent' C activation. In an attempt to clarify these disparate findings, we investigated the effect of several variables on C activation by HIV-infected cells using flow cytometric analysis of C3 deposition. Antibody-mediated C activation using pooled sera from infected persons or human MoAbs directed against the V3 region of gpl20 was always substantially higher than activation without antibody. Normal human serum (NHS) from a subset of HIV antibody-negative donors did. however, induce low levels of C3 deposilion. Differences in C3 activation between the various NHS did not correlate with total haemolytic C levels or mannose-binding protein (MBP) levels. IgM isolated from NHS that induced high levels of C activation was at least partly responsible for the 'antibody-independent* C activation. Although there appeared to be a correlation between NHS that induced C activation and the presence of anti-blood type B IgM. absorption of anti-B did not abrogate the C3 deposition. Additionally. MoAb to the B antigen did not induce C3 deposition. These studies show that IgM in sera from HI V-uninfected donors can induce C3 deposition on HIV-infected cells, but that specific anti body-dependent C activation is substantially more efficient. Therefore, "antibody-independent' C activation on HIV-infected cells may. in some cases, be more accurately described as HI V-crossreactive antibody-dependent C activation.

show abstract

“…Several reports have indicated that the complement system, either independently or in the presence of antibody, plays an important role in the host defense against viral infection (20,25). Direct Cl binding and classical pathway activation are mediated by specific sites in gp41 (9,34), and an alternative pathway is also activated by deposition of C3b on virus-infected cells (30). An important event of biological significance is associated with MAC and subsequent lysis of lipid bilayers (7).…”

Section: Discussionmentioning

confidence: 99%

Quantification of the CD55 and CD59, Membrane Inhibitors of Complement on HIV‐1 Particles as a Function of Complement‐Mediated Virolysis

Nakamura

Okada

Sasaki

et al. 1996

Microbiology and Immunology

View full text Add to dashboard Cite

Previous studies have demonstrated that the murine monoclonal antibody (MoAb) NM-01 activates the human complement classical pathway resulting in lysis of human immunodeficiency virus (HIV). The present study was performed to determine the availability of the V3-loop of gp120 relative to the complement regulatory proteins, CD55 (DAF) and CD59 (HRF20) molecules on HIV. The results demonstrate that CD55 and CD59 exist on HIV virions, along with gp120 molecules. These findings suggest that activation of human complement on free viral particles is induced by MoAb NM-01 and that this occurs regardless of the presence of CD55 and CD59 molecules. The destruction of viral particles was demonstrated by a decrease in infectivity. The involvement of human complement in this process was confirmed with an immunoelectron microscopy technique by the presence of a human C9 to prove membrane attack complex (MAC). The results indicate that NM-01 can induce complement activation because of the ratios of CD55 and CD59 to gp120 molecules on HIV virions. The availability of the gp120 V3 domain on the virion is sufficient for binding of NM-01 and thereby the formation of MAC that results in virolysis.

show abstract

HIV and HIV-infected cells differentially activate the human complement system independent of antibody

Cited by 77 publications

References 21 publications

Complement Mediates the Binding of HIV to Erythrocytes

Complement Mediates the Binding of HIV to Erythrocytes

Efficacy of HIV-specific and ‘antibody-independent’ mechanisms for complement activation by HIV-infected cells

Quantification of the CD55 and CD59, Membrane Inhibitors of Complement on HIV‐1 Particles as a Function of Complement‐Mediated Virolysis

Contact Info

Product

Resources

About