Identification of Human Cytomegalovirus strain with immediate-early (IE) antigen-specific monoclonal antibody is prevented by point mutation in the IE gene

In an AIDS patient with a disseminated human cytomegalovirus (HCMV) infection, presence of HCMV in blood was repeatedly excluded by the shell vial culture method with the HCMV immediate-early (IE) antigen-specific monoclonal antibody (MAb) 5D2 currently employed for rapid HCMV identification, whereas it was repeatedly confirmed by all other assays (conventional virus isolation from blood, antigenemia, and DNAemia). Sequence analysis of the HCMV strain revealed a point mutation in exon 2 of the IE gene, which led to a serine-to-proline substitution at position 20 of the corresponding protein. Cloning and expression of a region of the IE gene containing the mutation showed that this was responsible for the lack of reactivity of MAb 5D2. A pool of IE antigen-reactive MAbs instead of a single MAb must be used for rapid HCMV identification to detect all viral strains.