| RRC ID |
89949
|
| 著者 |
Arii J, Aktar S, Huang JR, Hirai M, Kawamura Y, Miura H, Wang B, Nagamata S, Nishimura M, Yoshikawa T, Harris RS, Mori Y.
|
| タイトル |
A viral APOBEC3 antagonist distinguishes HHV-6A from HHV-6B.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
17(1)
|
| 公開日 |
2026-5-1
|
| DOI |
10.1038/s41467-026-71951-6
|
| PII |
10.1038/s41467-026-71951-6
|
| PMID |
42067535
|
| PMC |
PMC13134964
|
| MeSH |
APOBEC Deaminases
Cytidine Deaminase* / antagonists & inhibitors
Cytidine Deaminase* / genetics
Cytidine Deaminase* / metabolism
Cytosine Deaminase* / genetics
Cytosine Deaminase* / metabolism
Genome, Viral
HEK293 Cells
Herpesvirus 6, Human* / genetics
Herpesvirus 6, Human* / physiology
Humans
Mutation
Roseolovirus Infections / virology
Viral Proteins / genetics
Viral Proteins / metabolism
Virus Replication
|
| リソース情報 |
| 研究用ヒト臍帯血幹細胞 |
|
