Identification of a 85 kDa phosphoprotein while an immunodominant protein specific for human being herpesvirus 7 infected cells

Identification of a 85 kDa phosphoprotein while an immunodominant protein specific for human being herpesvirus 7 infected cells. to pp85(U14). Here, the HHV-7-specific epitope in pp85(U14) was finely mapped to the C terminal region between amino acid residues 484 and 502. However, as indicated by the low level of reactivity of human being sera with the HHV-7-specific epitope identified by MAb 5E1, human being sera recognize additional epitopes of pp85(U14) that are required for their full reactivity. Primary illness with human being herpesvirus 7 (HHV-7) happens in infancy and is occasionally associated with exanthem subitum or fever without rash BMN-673 8R,9S (1, 6, 20, 22). More severe complications BMN-673 8R,9S of main HHV-7 infection include encephalitis and seizures due to invasion of the central nervous system (21). In healthy children and adults, the virus is definitely excreted in saliva, which is the most likely route of transmission (2, 8, 12, 23). In the general human population, HHV-7 seroprevalence reaches at least 80% (3, 6, 24). Until today, HHV-7 offers generally been regarded as an orphan disease that is not usually pathogenic beyond the self-limiting child years disease. However, more recently it has been BMN-673 8R,9S found that HHV-7 illness or reactivation is definitely associated with an increased risk of progression to cytomegalovirus (CMV) disease in renal transplant recipients positive for human being CMV (HCMV) (15), with a reduced survival time, and with an acute Rabbit Polyclonal to SFRS15 graft-versus-host disease in bone marrow transplant recipients (7). Therefore, HHV-7 only or in combination with additional -herpesviruses may be an important cofactor for the development of severe disease in immunosuppressed individuals. A specific analysis of illness with HHV-7 is needed (we) for children presenting with complications of primary illness in order to distinguish rash caused by HHV-7 from rashes caused by human being herpesvirus 6 (HHV-6), measles disease, and the disease that causes rubella or from an adverse reaction to antibiotic treatment (3); (ii) for immunocompromised adults, mainly transplant recipients, to assess the association between the virus and medical manifestations and to monitor the effect of antiviral therapy; and (iii) for accurate seroprevalence studies. Serologic analysis of HHV-7 illness poses a major problem of specificity because HHV-7 shares the same overall genome corporation with HHV-6, with homologies varying from 41 to 75% (11, 14, 17). As a result, some polyclonal antibodies and monoclonal antibodies (MAbs) directed to one disease cross-react with the additional virus. Cross-reacting HHV-7 and HHV-6 antibodies will also be present in human being sera. They can be eliminated by preabsorption with the heterologous HHV-6 antigens (4, 19). However, this is a bothersome procedure that is not readily reproducible and it is unavailable to the vast majority of diagnostic laboratories, because it requires routine growth of these viruses. In addition, preabsorption decreases the sensitivities of the assays. In studies in which different assays were compared and in which the reactivity of human being sera following preabsorption with heterologous HHV-6 antigen was analyzed, it was observed that immunoblotting is the most specific assay for detection of HHV-7 antibodies (4). Ninety percent of the sera reactive to HHV-7-infected cell lysates identified a protein with apparent molecular mass of 89 kDa (this protein was estimated to be 85 kDa inside a different laboratory; therefore, it is designated 85-89 kDa herein). Most importantly, reactivity with this protein was not affected by preabsorption with heterologous HHV-6 antigen (4, 10). These findings suggested that a protein of 85-89 kDa is definitely a specific determinant and marker of HHV-7 illness (4, 10). It has not been ascertained whether the 85-89-kDa protein represents one or multiple peptides. Two times bands were observed in some instances (4). Two BMN-673 8R,9S further findings are relevant to the present study. First, an HHV-7 85-kDa tegument phosphoprotein (pp85) offers been shown to be encoded from the U14 gene (19). MAb 5E1 is definitely directed to an HHV-7-specific epitope, which has not so much been mapped. Second, the immunodominant proteins p100 and pp150 of two additional -herpesviruses, HHV-6 and HCMV, are encoded by homologous genes, U11 and UL37, respectively (13, 25). The homologous gene of HHV-7 (U11) encodes a protein of 755 residues, having a determined molecular mass of 86 kDa (14). Therefore, the BMN-673 8R,9S mass and properties of the HHV-7 U14 and U11 gene products make both proteins likely candidates for the immunoreactive 85-89-kDa protein. The objective of this study was to identify the HHV-7 gene(s) that encodes the 85-89-kDa immunodominant protein(s) of HHV-7 and.