From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: HIV Infection through CR Receptor
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6676
Organization: unspecified
Date: Fri, 25 Dec 92 11:36:42 PST

Previous studies have shown that HIV-antibody immune complexes can 
infect cells the the Fc or Immunoglobulin receptor. These studies show that
immune complexes in the presence of complement can infect cells through the CR
or complement receptor.

More reasons why I think the present vaccine focus on antibodies is 
fraught with problems. 
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Montefiori DC, Zhou J, Shaff DI. CD-independent binding of HIV-1 to the 
B lymphocyte receptor CD2 (CD21) in the presence of complement and 
antibody. Clinical and Experimental Immunology 12/92; 90:383-389.

Abstract: Complement and antibody contribute to infection-enhancement 
and possible expanded cellular tropism of HIV-1 in vitro through a 
process requiring complement receptors. Until now, however, the ability 
of HIV-1 to bind complement receptors has not been documented or 
characterized. We investigated whether antibody and complement permitted 
HIV-1 to bind to the B lymphocytes receptor, CD2 (CD21), in an effort to 
learn more about infection-enhancement, and also because CD2 can mediate 
B cell proliferation and antigen localization in lymphoid organs in 
other systems. HIV-1 incubated with antibody and fresh human serum as a 
source of complement bound approximately 10-fold greater to cells 
expressing CR2 than to HIV-1 permissive cells lacking this receptor. A 
similar effect was observed using cells which expressed CR2 but no CD4. 
This binding was minimal in heat-inactivated and C3-deficient sera, and 
was significantly reduced by the anti-CD2 MoAb, OKB7, but not by the 
anti-CD4 MoAb, OKT4a. Thus, complement and antibody acted in concert to 
facilitate the binding of HIV-1 to CR2 independently of CD4. CD4- 
independent binding of HIV-1 to CR2 was not sufficient to produce 
infection in Raji-3 cells. Titres of antibodies mediating CD2 binding 
correlated with antibody titres as measured by immunofluorescence 
(P<0.01) and infection-enhancement (P<0.05) but were discordant with 
titres of neutralizing antibodies, a result consistent with the 
utilization of CD2 for enhanced infection of cells. The ability of 
complement and antibody to facilitate the binding of HIV-1 to CD2 in the 
absence of CD4 provides new insights into mechanisms of HIV-1-induced 
immunopathogenesis and infection-enhancement.
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Bakker LJ; Nottet HS; de Vos NM; de Graaf L; Van Strijp JA; Visser MR; 
Verhoef J. Antibodies and complement enhance binding and uptake of HIV-1 
by human monocytes. Aids, 1992 Jan, 6(1):35-41.                      
                                                                      
Abstract: OBJECTIVE: To characterize antibody- and complement-mediated 
binding and uptake of HIV-1 by human monocytes. DESIGN: The first step 
in the  infection of the monocyte by HIV-1 is binding of the virus to 
the susceptible cell. Procedures were designed to assess the influence 
of anti-HIV-1 antibodies and complement on this binding, and to study 
the process of internalization following binding. METHODS: Human 
monocytes were incubated with fluorescein-labelled purified HTLV-IIIB 
virions and human sera with high-titre anti-HIV-1 antibodies and/or 
complement. Binding and uptake of virus by the monocytes was measured as 
fluorescence per cell by flow cytometry. RESULTS: Binding of purified 
HIV-1 to monocytes was increased by complement and, to a lesser extent, 
by anti-HIV-1 antibodies. Uptake of HIV-1 bound to the monocyte appeared 
to be mediated by antibodies and was increased further by the presence 
of complement. Complement alone, however, resulted in the uptake of only 
a small part of the bound virus. CONCLUSIONS: Complement significantly 
increases the binding of HIV-1 to human monocytes, and a combination of 
antibodies and complement efficiently mediates uptake of HIV-1 by 
monocytes.
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June RA; Schade SZ; Bankowski MJ; Kuhns M; McNamara A; Lint TF; Landay 
AL; Spear GT. Complement and antibody mediate enhancement of HIV 
infection by increasing virus binding and provirus formation. AIDS, 1991 
Mar, 5(3):269-74.                                        
                                                                               
Abstract: Previous studies have shown that infection of complement 
receptor (CR2)-bearing cells with HIV pretreated with antibody (Ab) plus 
complement (C) resulted in increased virus expression. The current study 
was designed to determine whether C-mediated 'enhancement' of HIV-1 
production was the result of increased virus infection of cells as 
assessed by provirus formation and virus binding. Virus was incubated 
with anti-HIV Ab and/or C and added to CR2-positive MT-2 cells. 
Increased virus expression by MT-2 cells correlated with increased 
numbers of HIV-immunofluorescent-positive cells at 24 and 48 h and 
higher levels of provirus detected 8-28 h after infection. MT-2 cells 
also bound threefold more Ab-plus-C-treated virus than untreated virus. 
Serial dilutions of C showed that high levels of C with Ab did not 
enhance but rather suppressed virus expression. Studies were also 
performed which showed that terminal C components C5 and C8 were
not necessary for the enhancing effect. The increased binding of C- 
coated HIV to CR-positive cells has important implications for the fate 
of virus in vivo.

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