From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: HIV Infection through Fc Receptor
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6677
Organization: unspecified
Date: Fri, 25 Dec 92 11:39:20 PST

Previous studies have shown that HIV-antibody immune complexes can 
infect cells through the CR or Complement receptor. These studies that 
show that immune complexes can infect cells through the Fc 
or Immunoglobulin Receptor.

More reasons why I think the present vaccine focus on antibodies is 
fraught with problems. 
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Haubrich RH; Takeda A; Koff W; Smith G; Ennis FA. 
Studies of antibody-dependent enhancement of human immunodeficiency 
virus (HIV) type 1 infection mediated by Fc receptors using sera from 
recipients of a recombinant gp160 experimental HIV-1 vaccine. 
Journal of Infectious Diseases, 1992 Mar, 165(3):545-8. 

Abstract: Subneutralizing concentrations of sera from human 
immunodeficiency virus (HIV)-1-infected patients augment HIV infection 
mediated by Fc receptor uptake by human monocytes and the monocytic cell 
line U937. Antibody-dependent enhancement (ADE) and neutralization 
activity were studied in the sera of HIV-1 antibody-negative volunteers 
who had been immunized with three 40-micrograms doses of a recombinant 
gp160 (rgp160) candidate HIV vaccine. Volunteers were vaccinated with 
rgp160 or a hepatitis B vaccine as a control on days 0, 30, and 180. 
Sera were obtained before and after three doses of vaccine and were 
tested for ADE and neutralization activity. Serum samples collected 
before vaccination showed neither neutralization nor ADE activity. 
Thirteen sera from volunteers who received gp160 and four from placebo 
recipients failed to show ADE. Three sera showed low levels of 
neutralization of strain IIIB of HIV. Vaccination with this dose of 
rgp160 produced neutralizing antibodies in some subjects but did not 
induce detectable enhancing antibodies. 
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Laurence J; Saunders A; Early E; Salmon JE. Human immunodeficiency 
virus infection of monocytes: relationship to Fc-gamma receptors and 
antibody-dependent viral enhancement.                               
Immunology, 1990 Jul, 70(3):338-43. 

Abstract: Antibodies that augment human immunodeficiency virus (HIV) 
infectivity of monocytes through Fc receptor (FcR) type III for IgG have 
been found in the blood of sero-positive patients and immunized 
chimpanzees. This study investigated the effect of acute and chronic 
HIV infection, as well as protein kinase C activators capable of up- 
regulating latent HIV, on the expression of these receptors. In 
addition, the frequency of this antibody-dependent enhancement (ADE) 
phenomenon was estimated using purified IgG from HIV-1 seropositive 
individuals at various clinical stages of infection. The existence of an 
FcR-dependent pathway for ADE of HIV-1 infection in peripheral blood 
monocytes and promonocytic U937 cells was confirmed in sera from a small 
subset of patients, and the phenomenon extended to FcR types I and II. 
The level of ADE activity was minimal, however, and no relationship 
between the presence or magnitude of the ADE phenomenon and clinical 
stage was uncovered. Finally, perturbations which activate a latent HIV 
infection were shown to concomitantly up-regulate FcR on infected and 
uninfected cells. This suggests a positive feedback loop linking up- 
regulation of latent infection, enhanced expression of low affinity HIV 
receptors such as FcR, and viral spread. 
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Robinson WE Jr; Montefiori DC; Gillespie DH; Mitchell WM. Complement- 
mediated, antibody-dependent enhancement of HIV-1 infection in vitro is 
characterized by increased protein and RNA syntheses and infectious 
virus release. Journal of Acquired Immune Deficiency Syndromes, 1989, 
2(1):33-42. 

Abstract: Antibody-dependent enhancement (ADE) of human immunodeficiency 
virus type 1 (HIV-1) infection in vitro has been described recently and 
was shown to occur by two mechanisms: either participation of the 
alternative pathway of complement or to involve an Fc receptor-mediated, 
complement-independent mechanism. Complement-mediated ADE results in an 
accelerated cytopathic effect in target cells that can abrogate the 
protective properties of neutralizing antibodies. This study 
characterizes the surface antigens of MT-2 cells using flow cytometric 
analysis and shows that these cells express high levels of both CD4 and 
complement receptor type 2 (CR2) while several CD4+ cell lines that do 
not demonstrate complement-mediated ADE lack high levels of complement 
receptors. Further, utilizing MT-2 cell cultures, it is demonstrated 
that complement-mediated ADE of HIV-1 infection is conferred by the sera 
from more than 80% of HIV-1 antibody-positive individuals (N = 85). 
Complement-mediated ADE of HIV-1 infection causes an acceleration of 
several parameters indicative of HIV-1 infection in vitro including 
increased HIV-1 antigen synthesis as detected by indirect 
immunofluorescence, RNA accumulation as measured by a solution 
hybridization protocol, reverse transcriptase release, and progeny virus 
production. 

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