Antigenic cross-reactions among herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus

Balachandran, N.; Oba, D E; Hutt-Fletcher, Lindsey

doi:10.1128/jvi.61.4.1125-1135.1987

Cited by 93 publications

(36 citation statements)

References 44 publications

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“…Monoclonal antibodies E1D1 and F-2-1 were gifts from L. Hutt-Fletcher (Louisana State University Health Sciences Center, Shreveport, La.) and recognize the gH/gL complex and gp42, respectively (1,44). A large-scale preparation of the E1D1 and the F-2-1 antibodies was made at the Northwestern University Monoclonal Antibody Facility.…”

Section: Methodsmentioning

confidence: 99%

The Amino Terminus of Epstein-Barr Virus Glycoprotein gH Is Important for Fusion with Epithelial and B Cells

Omerović

Lev

Longnecker

2005

J Virol

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Epstein-Barr virus (EBV) infects B lymphocytes and epithelial cells. While the glycoproteins required forentry into these two cell types differ, the gH/gL glycoprotein complex is essential for entry into both epithelial and B cells. Analysis of gH protein sequences from three gammaherpesviruses (EBV, marmoset, and rhesus) revealed a potential coiled-coil domain in the N terminus. Four leucines located in this region in EBV gH were replaced by alanines by site-directed mutagenesis and analyzed for cell-cell membrane fusion with B cells and epithelial cells. Reduction in fusion activity was observed for mutants containing L65A and/or L69A mutations, while substitutions in L55 and L74 enhanced the fusion activity of the mutant gH/gL complexes with both cell types. All of the mutants displayed levels of cell surface expression similar to those of wild-type gH and interacted with gL and gp42. The observation that a conservative mutation of leucine to alanine in the N terminus of EBV gH results in fusion-defective mutant gH/gL complexes is striking and points to an important role for this region in EBV-mediated membrane fusion with B lymphocytes and epithelial cells. Epstein-Barr virus (EBV) is a gammaherpesvirus that has tropism for both B lymphocytes and epithelial cells (18, 42).Similar to other enveloped viruses, EBV entry into the target cells occurs in two steps: the initial attachment of the virus to the cell surface and the subsequent fusion of the viral envelope and the cell membrane (18, 51). EBV infection can occur by cell-free virus or through cell-cell spread, but fusion is required for both entry pathways (18, 42). The initiation of infection by EBV is driven by interaction of viral glycoproteins with cellsurface receptors (42). EBV encodes as many as 11 glycoproteins, but only a subset is required for efficient EBV entry (15,42). In general, more is known about the mechanism of EBV entry into B lymphocytes than into epithelial cells. Infection of B lymphocytes is initiated by the attachment of glycoprotein gp350/220 to the CD21/CR2 receptor on the B cells (9,43,45). This interaction enhances infection efficiency of B cells, but it is not absolutely required for infection to occur (16). Subsequent to this binding, viral glycoprotein gp42 binds to the B-cell surface protein HLA class II, which triggers fusion mediated by a concerted action of three glycoproteins (gB, gH, and gL) (19,43). The glycoprotein requirement for EBV entry differs between epithelial and B cells; gB, gH, and gL are essential for infection of both epithelial and B cells, while gp42 is required only for B-cell entry (12,20,24,47). Even though gB, gH, and gL are conserved throughout the herpesvirus family, the structure and the exact mechanism of action of these three glycoproteins in the fusion process are still unclear.

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Section: Methodsmentioning

confidence: 99%

The Amino Terminus of Epstein-Barr Virus Glycoprotein gH Is Important for Fusion with Epithelial and B Cells

Omerović

Lev

Longnecker

2005

J Virol

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“…The presence of a strong human-antibody response, with both HCMV' and EBV' human sera, against the sequence TVDSMIALDI (positions 643 -652) is clearly evident; it has to be emphasized that that this major antibody-binding fragment is not included in the region covered by the set of peptides used in previous studies [29]. Several examples of monoclonal antibodies and animal sera recognizing HSV gB and the corresponding proteins of other herpes viruses have been described [20]. Cross-reactivity among herpes viruses has also been observed for human sera [25].…”

Section: Discussionmentioning

confidence: 98%

“…glycoprotein C: AD-1, antigenic domain-I of gp58.coproteins, namely the Epstein-Barr-virus (EBV) and herpessimplex-virus (HSV) glycoprotein B (gB), and varicella-herpes-zoster-virus (VHZV) glycoprotein 11, whose role in eliciting a host-immune response has been clearly shown [lo, 17-191. Since cross-reactions of antisera directed against these proteins have been described [20], this feature must be considered for a detailed analysis of HCMV gp58 antigenic properties. These studies are significant, since it has been recently shown that the majority of neutralizing activity in convalescent-human serum is directed against gCI [21], and the isolated complex is also able to induce both humoral and cellular-immune responses in human volunteers [22].In previous studies a HCMV gp58 linear antigenic site, recognized by neutralizing antibodies, has been identified near amino acid 616 by the use of recombinant gp58-fusion proteins.…”

mentioning

confidence: 99%

Characterization of immunoreactive octapeptides of human‐cytomegalovirus gp58

Bonci

Bracci

Caudai

et al. 1993

European Journal of Biochemistry

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We have mapped continuous epitopes, for positions 591 -673 of the human cytomegalovirus 58-kDa glycoprotein using overlapping synthetic peptides and human sera. This region contains a fragment previously described as including the dominant site for induction of human-cytomegalovirus antibodies. Since the selected sequence is highly conserved among herpes viruses, we have considered the possible presence of antigenic cross-reactivity, particularly with the Epstein-Barr virus. Several peptides in the studied region were antigenic and two main continuous epitopes have been identified. Serological cross-reactions observed with Epstein-Barr virus are discussed, focussing on the possible implications of structural features and sequence similarity between humancytomegalovirus and Epstein-Barr-virus glycoproteins.Human-cytomegalovirus (HCMV) infections play an important role as a source of human disease; although primary infection is usually mild or asymptomatic the virus is a major pathogen in immunocompromised individuals and a common cause of congenital defects [l]. A more detailed understanding of the antigenic features involved in the human immune response against HCMV would allow for better control and detection of this infection in susceptible hosts.The HCMV genome codes for 35 -45 structural proteins, most of which are immunogenic [2-41. Outer-envelope glycoproteins, in particular, seem to be major targets for viral neutralization. In several reports, monoclonal antibodies have been described that react with HCMV glycoproteins [5-71, and individually purified or expressed glycoproteins have also been shown to elicit neutralizing responses in experimental animals [8-111. HCMV glycoproteins have been recently grouped into three distinct families, designated gCI-gCIII [ 121. gCI is the major envelope component, consisting of two disulphidelinked protein species of estimated molecular mass 55-58 kDa and 100-116 kDa [13]; these mature forms are generated by proteolytic cleavage of a high-molecular-mass precursor, which is both co-translationally and post-translationally glycosylated [ 14-161.The gene encoding the 58-kDa glycoprotein (gp58) has been mapped and sequenced [ 10, 171 ; the translational product shows sequence similarity with other herpes-virus gly- coproteins, namely the Epstein-Barr-virus (EBV) and herpessimplex-virus (HSV) glycoprotein B (gB), and varicella-herpes-zoster-virus (VHZV) glycoprotein 11, whose role in eliciting a host-immune response has been clearly shown [lo, 17-191. Since cross-reactions of antisera directed against these proteins have been described [20], this feature must be considered for a detailed analysis of HCMV gp58 antigenic properties. These studies are significant, since it has been recently shown that the majority of neutralizing activity in convalescent-human serum is directed against gCI [21], and the isolated complex is also able to induce both humoral and cellular-immune responses in human volunteers [22].In previous studies a HCMV gp58 linear antigenic site, recogniz...

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“…La recherche d'anticorps hétérophiles et d'anticorps spécifiques contre les antigènes du virus d'Epstein Barr est utile pour le diagnostic d'une infection aiguë surtout en présence d'un haut index de suspicion clinique [7]. Toutefois une possible réaction croisée avec la sérologie du CMV nécessite une interprétation avec précaution [8]. Chez notre malade, l'évolution temporelle de ces sérologies pouvait aider à discerner entre les deux virus.…”

Section: Discussionunclassified