During hepatitis B virus (HBV) infection, high numbers of non-infectious HBV surface antigen (HBsAg) particles are present in circulation. It is shown here that recombinant HBsAg (rHBsAg) particles, which contain the S protein only, bind almost exclusively to monocytes. Attachment of rHBsAg to the THP-1 pre-monocytic cell line occurs upon 1,25-dihydroxyvitamin D3-induced differentiation. Binding to monocytes is enhanced by a heat-labile serum protein and is inhibited by Ca2+/Mg2+, low pH and an HBsAg-specific monoclonal antibody. Furthermore, it is shown that rHBsAg suppresses lipopolysaccharide- and IL-2-induced production of cytokines. These results suggest the existence of a monocyte-specific receptor, the engagement of which by HBsAg suppresses the activity of these cells.
AkbarS. M.,
OnjiM.,
InabaK.,
YamamuraK.-I.,
OhtaY.1993; Low responsiveness of hepatitis B virus-transgenic mice in antibody response to T-cell-dependent antigen: defect in antigen-presenting activity of dendritic cells. Immunology 78:468–475
BoscoM. C.,
Espinoza-DelgadoI.,
RoweT. K.,
MalabarbaM. G.,
LongoD. L.,
VaresioL.1997; Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2. Journal of Immunology 159:2922–2931
BudkowskaA.,
QuanC.,
GrohF.,
BedossaP.,
DubreuilP.,
BouvetJ. P.,
PillotJ.1993; Hepatitis B virus (HBV) binding factor in human serum: candidate for a soluble form of hepatocyte HBV receptor. Journal of Virology 67:4316–4322
GagliardiM. C.,
NisiniR.,
BenvenutoR.,
De PetrilloG.,
MichelM. L.,
BarnabaV.1994; Soluble transferrin mediates targeting of hepatitis B envelope antigen to transferrin receptor and its presentation by activated T cells. European Journal of Immunology 24:1372–1376
GanemD.1996; Hepadnaviridae and their replication. In Fields Virology pp 2703–2738 Edited by
FieldsB. N.,
KnipeD. M.,
HowleyP. M.
Philadelphia: Lippincott–Raven;
ImaiM.,
YanaseY.,
NojiriT.,
MiyakawaY.,
MayumiM.1979; A receptor for polymerized human and chimpanzee albumins on hepatitis B virus particles co-occurring with HBeAg. Gastroenterology 76:242–247
JochumC.,
VothR.,
RossolS.,
Meyer zum BuschenfeldeK. H.,
HessG.,
WillH.,
SchroderH. C.,
SteffenR.,
MullerW. E.1990; Immunosuppressive function of hepatitis B antigens in vitro : role of endoribonuclease V as one potential trans inactivator for cytokines in macrophages and human hepatoma cells. Journal of Virology 64:1956–1963
KuroseK.,
AkbarS. M.,
YamamotoK.,
OnjiM.1997; Production of antibody to hepatitis B surface antigen (anti-HBs) by murine hepatitis B virus carriers: neonatal tolerance versus antigen presentation by dendritic cells. Immunology 92:494–500
MullerC.,
ZielinskiC. C.1990; Impaired lipopolysaccharide-inducible tumor necrosis factor production in vitro by peripheral blood monocytes of patients with viral hepatitis. Hepatology 12:1118–1124
MullerC.,
ZielinskiC. C.1992; Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. Journal of Hepatology 15:372–377
NeurathA. R.,
StrickN.,
SproulP.1992; Search for hepatitis B virus cell receptors reveals binding sites for interleukin 6 on the virus envelope protein. Journal of Experimental Medicine 175:461–469
PaulijW. P.,
de WitP. L. M.,
SünnenC. M. G.,
van RoosmalenM. H.,
Petersen-van EttekovenA.,
CooremanM. P.,
HeijtinkR. A.1999; Localization of a unique hepatitis B virus epitope sheds new light on the structure of hepatitis B virus surface antigen. Journal of General Virology 80:2121–2126
PedronT.,
GirardR.,
ChabyR.1995; Variation of LPS-binding capacity, epitope expression, and shedding of membrane-bound CD14 during differentiation of human monocytes. Journal of Immunology 155:1460–1471
PontissoP.,
MorsicaG.,
RuvolettoM. G.,
ZambelloR.,
CollettaC.,
ChemelloL.,
AlbertiA.1991; Hepatitis B virus binds to peripheral blood mononuclear cells via the pre S1 protein. Journal of Hepatology 12:203–206
StrickerE. A. M.,
TieboutR. F.,
LelieP. N.,
ZeijlemakerW. P.1985; A human monoclonal IgG1λ anti-hepatitis B surface antibody. Production, properties, and application. Scandinavian Journal of Immunology 22:337–343