Human herpesvirus 6 U11 protein is critical for virus infection

Abstract

All herpesviruses contain a tegument layer comprising a protein matrix; these proteins play key roles during viral assembly and egress. Here, liquid chromatography and tandem mass spectrometry analysis (LC-MS/MS) of proteins from human herpesvirus 6 (HHV-6)-infected cells revealed a possible association between two major tegument proteins, U14 and U11. This association was verified by immunoprecipitation experiments. Moreover, U11 protein was expressed during the late phase of infection and incorporated into virions. Finally, in contrast to its revertant, a U11 deletion mutant could not be reconstituted. Taken together, these results suggest that HHV-6 U11 is an essential gene for virus growth and propagation.

Crystal Structure of Human Herpesvirus 6B Tegument Protein U14

“…In the case of HHV-7, U14 is known as a major antigen pp85 [ 33 ], and U14 is thought to be relatively expressed abundantly. On the other hand, one of predominant major antigens of HHV-6 has been shown to be U11 [ 34 ], [ 35 ], which has been revealed to interact with U14 [ 36 ]. It may be noteworthy to mention that the HCMV UL25 was expressed abundantly especially in the dense body [ 37 ].…”

“…Another possibility is that the β hairpin is involved in binding to other viral proteins, such as tegument proteins to form the tegument structure or capsid or envelope proteins to form the virion structure. Recently, we identified a major tegument U11 as the binding partner of U14 [ 36 ], then the effect of the mutation/deletion on the β hairpin was also analyzed by the immunoprecipitation assay ( S6 Fig ). The interaction between U14 and U11 was abolished by the deletion of the corresponding residues of the L424, E425 and V426.…”

“…Thus, we suggest that the β hairpin is the binding site for U11 and the exposed hydrophobic sidechain of I414 observed in the U14-NTD structure is likely to be recognized by U11. Because U11 is an abundant and essential tegument protein of HHV-6 [ 36 ], further research focused on the interaction via the β hairpin will provide more information about the functionality of U14.…”

HLA-A∗02, gender and tobacco smoking, but not multiple sclerosis, affects the IgG antibody response against human herpesvirus 6

“…Another gene with high divergence between HHV-6A and HHV-6B is the late gene U11 that codes for p100 in HHV-6A and 101K in HHV-6B, two tegument proteins with 81% amino acid identity [51]. These structural proteins are essential for virus growth and propagation [52] and 101K has been demonstrated to be a highly immunoreactive protein that is the dominant antigen recognized by HHV-6A/6B IgG [53].…”

Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis

“…The ORF U11 coding for p100 in HHV-6A and 101K in HHV-6B also exhibit relatively high divergence with only 81% amino acid identity (40). These structural proteins are essential for viral growth and propagation (41), and 101K has been identified as the dominant antigen recognized by anti-HHV-6B IgG (42). With the aim to discriminate between IgG responses against these two viruses, we developed a novel bead-based multiplex serology assay measuring IgG antibodies against IE1A, IE1B, p100, and 101K, selecting the most divergent parts of these protein sequences.…”