NetNews Usenet Archive 1992 #31/NN_1992_31.iso/spool/sci/med/aids/2164

Text File | 1992-12-25 | 5.9 KB | 99 lines

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From: Billi Goldberg <[e-mail]>
Subject: HIV Infection through CR Receptor
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Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
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Date: Fri, 25 Dec 92 11:36:42 PST
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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.