Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The VSports app下载. gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

. 2006 Oct;80(19):9628-33.
doi: 10.1128/JVI.00622-06.

Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells

Susan M Turk  1 , Ru Jiang, Liudmila S Chesnokova, Lindsey M Hutt-Fletcher
Affiliations

Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells (V体育官网)

Susan M Turk et al. J Virol. 2006 Oct.

Abstract

Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma. We report here that antibodies to gp350/220, which inhibit EBV infection of B cells, enhance infection of epithelial cells. The effect is not mediated by Fc receptor binding but is further enhanced by antibody cross-linking, which may patch gp350/220 in the virus envelope. Saliva from EBV-seropositive individuals has similar effects that can be reversed by depletion of antibody. The results are consistent with a model in which gp350/220 interferes with the access of other important players to the epithelial cell surface. The results may have implications for the development of nasopharyngeal carcinoma in high-risk populations in which elevated titers of antibody to EBV lytic cycle proteins are prognostic VSports手机版. .

PubMed Disclaimer

VSports手机版 - Figures

FIG. 1.
FIG. 1.
Antibodies to glycoprotein gp350/220 enhance infection of CD21-negative epithelial cells. AGS epithelial cells infected with recombinant EBV expressing GFP that had been preincubated with medium alone (none), with two MAbs to gp350/220 (gp350), or with two nonneutralizing antibodies to glycoprotein gB (gB). The percentage of cells infected was determined by counting those expressing GFP at 48 h postinfection. Error bars indicate the standard deviation of seven separate experiments.
FIG. 2.
FIG. 2.
MAbs to gp350/220 lacking an Fc domain can inhibit B-cell infection and enhance epithelial cell infection, but only if they are bivalent. AGS epithelial cells or EBV-negative Akata B cells were infected with recombinant virus expressing GFP after preincubation with medium alone (none), intact antibodies (ab), or F(ab′)2 fragments (A) or with medium alone, intact antibodies, Fab fragments (Fab), or Fab fragments cross-linked by addition of anti-mouse antibody (Fab + anti-mse) (B). Error bars indicate standard deviation of three (A) or two (B) separate experiments. Different virus pools were used in panels A and B.
FIG. 3.
FIG. 3.
Addition of soluble protein A/G to MAbs to gp350/220 increases their ability to enhance infection of epithelial cells. AGS epithelial cells were infected with recombinant EBV expressing GFP that had been preincubated with medium alone (none), with two MAbs to gp350/220 (gp350), or with two MAbs to gp350/220 and 100 μg of soluble protein A/G (gp350 + prot AG). Error bars indicate the standard deviation of five separate experiments.
FIG. 4.
FIG. 4.
MAbs to gp350/220, but not antibodies to gB, enhance infection of CD21-positive 293 cells. 293 cells were infected with recombinant EBV expressing GFP that had been preincubated with medium alone (none), with two MAbs to glycoprotein gB (gB), with two MAbs to gB and 100 μg of soluble protein A/G (gB + prot AG), with two MAbs to gp350/220 (gp350), or with two MAbs to gp350/220 and 100 μg of soluble protein A/G (gp350 + prot AG). Error bars indicate the standard deviation of four infections in two separate experiments.
FIG. 5.
FIG. 5.
Enhanced infection is not a result of increased binding of virus and is not influenced by preincubation of AGS epithelial cells with antibody to α5β1 integrins. (A) Virus preincubated in medium (none), MAbs to gp350/220 (gp350), or MAbs to gB (gB) was incubated on ice for 2 h with cells or cells preincubated with antibody to α5β1 integrins (gp350 + integrin). Cells were then washed, and relative amounts of virus bound per cell were measured by real-time quantitative PCR for the BamHI K fragment of EBV and for cellular CRP. Virus bound, in arbitrary (arb.) units, represents the values obtained for EBV divided by the values obtained for CRP expressed relative to virus binding in the absence of antibody (set at 100). (B) AGS cells infected with recombinant EBV expressing GFP that had been preincubated with medium alone (none), with two MAbs to gp350/220 and AGS cells preincubated with antibody to α5β1 integrins before infection with virus bound to antibodies to gp350/220 (gp350 + integrin). Error bars indicate the standard deviation of six experiments. None of the values in panel A were statistically significantly different (P < 0.1), and in panel B the values for gp350 and gp350 + integrin were not significantly different (P < 0.1).
FIG. 6.
FIG. 6.
Saliva from seropositive, but not seronegative, individuals inhibits B-cell infection and enhances epithelial cell infection, and antibody depletion partially reverses these effects. (A) EBV-negative Akata B cells or AGS epithelial cells infected with virus preincubated with medium (none) with saliva or with saliva from which antibody had been deleted by preabsorption with immobilized protein A (absorbed saliva). (B) EBV-negative Akata B cells or AGS epithelial cells infected with virus preincubated with medium (none) or with saliva from seropositive or seronegative donors as indicated. Error bars indicate the standard deviation of four donors. All saliva was clarified by centrifugation at 16,000 × g for 1 h and filtered through a 0.2-μm-pore-size filter before use. The experiments whose results are shown in panels A and B were done with different virus pools.
See this image and copyright information in PMC

"V体育安卓版" References

    1. Borza, C. M., and L. M. Hutt-Fletcher. 2002. Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat. Med. 8:594-599. - PubMed
    1. Borza, C. M., A. J. Morgan, S. M. Turk, and L. M. Hutt-Fletcher. 2004. Use of gHgL for attachment of Epstein-Barr virus to epithelial cells compromises infection. J. Virol. 78:5007-5014. - PMC - PubMed
    1. Chan, A. S. C., K. F. To, K. W. Lo, K. F. Mak, W. Pak, B. Chiu, G. M. K. Tse, M. Ding, X. Li, J. C. K. L. Lee, and D. P. Huang. 2000. High frequency of chromosome 3p deletion in histologically normal nasopharyngeal epithelia from southern Chinese. Cancer Res. 60:5365-5370. - PubMed
    1. Fingeroth, J. D., M. E. Diamond, D. R. Sage, J. Hayman, and J. L. Yates. 1999. CD21-dependent infection of an epithelial cell line, 293, by Epstein-Barr virus. J. Virol. 73:2115-2125. - PMC - PubMed
    1. Fingeroth, J. D., J. J. Weis, T. F. Tedder, J. L. Strominger, P. A. Biro, and D. T. Fearon. 1984. Epstein-Barr virus receptor of human B lymphocytes is the C3d complement CR2. Proc. Natl. Acad. Sci. USA 81:4510-4516. - PMC - PubMed

Publication types

MeSH terms