A viral APOBEC3 antagonist distinguishes HHV-6A from HHV-6B

Nature Communications 2026 Open access

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Authors: Jun Arii, Salma Aktar, Jing Rin Huang, Mansaku Hirai, Yoshiki Kawamura, Hiroki Miura, Bochao Wang, Satoshi Nagamata, Mitsuhiro Nishimura, Tetsushi Yoshikawa, Reuben S. Harris, Yasuko Mori
DOI: 10.1038/s41467-026-71951-6
Cited by: 1
References: 74

Abstract

Human herpesviruses exhibit diverse pathogenic outcomes and the molecular reasons are not fully understood. Human herpesvirus 6B (HHV-6B) causes exanthema subitum and encephalitis, whereas the closely related HHV-6A is typically asymptomatic. Here, we show that cellular APOBEC3 enzymes restrict HHV-6A replication but not HHV-6B. HHV-6B expresses higher levels of the U28 protein, which binds multiple APOBEC3 proteins and promotes their relocalization and degradation. In contrast, HHV-6A fails to counteract APOBEC3 activity and accumulates extensive mutations in both cell- and patient-derived viral genomes. Individual APOBEC3 gene ablation enhances HHV-6A replication and reduces the viral mutation burden. Together, our studies suggest that differential susceptibility to APOBEC3 restriction may help to shape the evolvability and clinical manifestations of HHV-6A and HHV-6B.

Fields of Study & Subjects

Cytomegalovirus and herpesvirus research Viral-associated cancers and disorders Herpesvirus Infections and Treatments

Publication details

Journal / source
Nature Communications
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Pages
3566
Publication date
1 May 2026
Language
EN