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Hepatitis B virus surface antigen suppresses the activation of monocyt...
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Hepatitis B virus surface antigen suppresses the activation of monocyte

http://vir.sgmjournals.org/content/83/6/1281.full.pdf

Discussion
Plasma-derived or recombinant HBsAg particles have been
used widely to identify cellular receptors for HBV attachment
and entry. Several receptors have been put forward but, so far,
convincing data to support these claims are lacking. Serum
proteins that bind to HBsAg were identi®ed as well. These
are thought to bridge virus and cellular receptors. Again,
data to support these possibilities are lacking. The possible
modulation by HBsAg of cellular and immunological responses
during HBV infection has received much less attention. It has
been speculated that the large number of HBsAg particles may
induce T cell anergy and may prevent antibody-mediated
neutralization of HBV. In vitro studies have demonstrated a
reduced capacity of PBMCs from chronically infected persons
to produce cytokines upon stimulation with LPS (Muller &
Zielinski, 1990, 1992). Moreover, ten years ago it was shown
that HBsAg can suppress the production by human macro-
phages of different cytokines induced by different agents such
as LPS, vesicular stomatitis virus and granulocyte-macrophage
colony-stimulating factor. A role for endoribonuclease V as a
post-transcriptional inactivator of cytokine transcripts was
demonstrated (Jochum et al., 1990). Taken together, these
results suggest that HBsAg interacts with one or more
receptors on antigen-presenting cells, like monocytes, macro-
phages and dendritic cells. Attachment of HBsAg to mono
cytes was reported previously, an interaction that was shown
to occur via pre-S1 (Pontisso et al., 1991; Neurath et al., 1992)
Data presented here clearly demonstrate that monocytes
express a receptor, which is recognized by ± S protein only ±
HBsAg expressed in yeast. Moreover, using THP-1 cells and
PMA-treated monocytes, it is shown that this receptor is
present in a more mature differentiation state only. Binding to
macrophages, obtained by culturing monocytes for 7 days,
was observed as well (data not shown). A protein present in HS
enhances attachment of rHBsAg to the plasma membrane of
monocytes. This protein is rapidly inactivated by incubation at
56 °C, a procedure routinely performed with sera used for
tissue culture. Binding of rHBsAg is partially inhibited by an S
protein-speci®c MAb (F47B), while F47B-dependent binding
to B cells is observed. When the same experiment was
performed with heat-inactivated serum, attachment of rHBsAg
to monocytes and B cells was observed, but only in the
presence of MAb F47B (data not shown). This observation
suggests that the complete inhibition of binding to monocytes
is masked, probably by the alternative attachment of rHBsAg±
antibody complexes to Fc receptors. The binding of rHBsAg to
B cells most probably results from such interactions as well.
Binding of b-rHBsAg was decreased in the presence of
Ca#+}Mg#+ and H+ (low pH).
To ®nd a possible biological function for this rHBsAg±
receptor interaction, the effect of rHBsAg on LPS- and IL-2-
induced activation of monocytes was investigated. One of the
most potent activators of monocytes is LPS, which induces the
secretion of several cytokines, such as IL-1b, IL-6, IL-12 and
TNFa rHBsAg particles themselves did not induce any of
these cytokines, while LPS-induced secretion of IL-1b and
TNFa was reduced in the presence of rHBsAg. Using
macrophages and plasma-puri®ed HBsAg, identical results for
TNFa have been reported previously. However, in contrast to
our results, human macrophages produced IL-1b in response to
HBsAg (Jochum et al., 1990). A second potent activator of
monocytes is IL-2, which, among several other activities,
increases the secretion of cytokines like IL-8, IL-6 and TNFa.
As shown previously (Bosco et al., 1997), blood monocytes
already secreted IL-8 when cultured without IL-2. This
production was downregulated by rHBsAg. More importantly,
IL-2-induced IL-8 secretion was reduced in the presence of
rHBsAg.
Viruses have long been viewed as simple genetic parasites
that use the host cellular machinery to propagate themselves.
However, it has become clear that the co-existence of these
pathogens and their hosts have shaped the immune system and
resulted in a surprising diversity of virus strategies to
manipulate different cellular and immune regulatory systems.
Viruses have targeted cellular cytokine production and cyto-
kine receptor-signalling pathways, apoptotic pathways, cell
growth and activation pathways, MHC-restricted antigen
presentation pathways and humoral immune responses (Alcami
et al., 2000; Tortorella et al., 2000). Our results sugges

strongly that monocytes express a receptor that is recognized
by HBsAg. Engagement of this receptor, through interaction
with a serum protein, suppresses the activity of monocytes.
These observations suggest that HBV produces HBsAg in
excess amounts to interfere with the normal function of
antigen-presenting cells
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i do hope gcmaf has a place in this scenario but this finding suggests gcmaf might be slower.......
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Avatar_m_tn
Good paper. It seems serum HBsAg and HBeAg, as studyforhope stated, both suppress our immune system. Good for the virus but bad for us.
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