Human herpesvirus 6 (HHV-6) is a β-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A/B show high genome homology and harbor the conserved U94 gene, which is limited to HHV-6 and absent in all the other human herpesviruses. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation. During natural infection, U94 elicits an immune response, and the prevalence and extent of the anti-U94 response are associated with specific diseases. Notably, U94 can entirely reproduce some virus effects at the cell level, including inhibition of cell migration, induction of cytokines and HLA-G expression, and angiogenesis inhibition, supporting a direct U94 role in the development of HHV-6-associated diseases. Moreover, specific U94 properties, such as the ability to modulate angiogenesis pathways, have been exploited to counteract cancer development. Here, we review the information available on this key HHV-6 gene, highlighting its potential uses.

The U94 gene of human herpesvirus 6: a narrative review of its role and potential functions

Elisabetta Caselli
Primo
Conceptualization
;
Maria D’Accolti
Secondo
Writing – Original Draft Preparation
;
Irene Soffritti;Valentina Gentili;Daria Bortolotti;Antonella Rotola;Enzo Cassai;Roberta Rizzo
Penultimo
;
Dario Di Luca
Ultimo
2020

Abstract

Human herpesvirus 6 (HHV-6) is a β-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A/B show high genome homology and harbor the conserved U94 gene, which is limited to HHV-6 and absent in all the other human herpesviruses. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation. During natural infection, U94 elicits an immune response, and the prevalence and extent of the anti-U94 response are associated with specific diseases. Notably, U94 can entirely reproduce some virus effects at the cell level, including inhibition of cell migration, induction of cytokines and HLA-G expression, and angiogenesis inhibition, supporting a direct U94 role in the development of HHV-6-associated diseases. Moreover, specific U94 properties, such as the ability to modulate angiogenesis pathways, have been exploited to counteract cancer development. Here, we review the information available on this key HHV-6 gene, highlighting its potential uses.
Caselli, Elisabetta; D'Accolti, Maria; Caccuri, Francesca; Soffritti, Irene; Gentili, Valentina; Bortolotti, Daria; Rotola, Antonella; Cassai, Enzo; Fiorentini, Simona; Zani, Alberto; Caruso, Arnaldo; Rizzo, Roberta; DI LUCA, Dario
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2443596
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