A Conserved Mechanism of APOBEC3 Relocalization by Herpesviral Ribonucleotide Reductase Large Subunits.
APOBEC Deaminases
Cell Line
Cytidine Deaminase
/ metabolism
Cytosine Deaminase
/ metabolism
HEK293 Cells
Herpes Simplex
Herpesviridae Infections
Herpesvirus 1, Human
/ metabolism
Herpesvirus 4, Human
/ metabolism
Herpesvirus 8, Human
/ metabolism
Host-Pathogen Interactions
Humans
Immunity, Innate
Minor Histocompatibility Antigens
/ metabolism
Proteins
/ metabolism
Ribonucleotide Reductases
/ metabolism
Viral Proteins
/ metabolism
Virus Replication
APOBEC3A
APOBEC3B
herpesviruses
innate antiviral immunity
ribonucleotide reductase
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
09
09
2019
accepted:
17
09
2019
pubmed:
20
9
2019
medline:
17
6
2020
entrez:
20
9
2019
Statut:
epublish
Résumé
An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes, such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B). The large subunit of the viral RNR, BORF2, causes A3B relocalization from the nucleus to cytoplasmic bodies and thereby protects viral DNA during lytic replication. Here, we use coimmunoprecipitation and immunofluorescence microscopy approaches to ask whether this mechanism is shared with the closely related gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) and the more distantly related alphaherpesvirus herpes simplex virus 1 (HSV-1). The large RNR subunit of KSHV, open reading frame 61 (ORF61), coprecipitated multiple APOBEC3s, including A3B and APOBEC3A (A3A). KSHV ORF61 also caused relocalization of these two enzymes to perinuclear bodies (A3B) and to oblong cytoplasmic structures (A3A). The large RNR subunit of HSV-1, ICP6, also coprecipitated A3B and A3A and was sufficient to promote the relocalization of these enzymes from nuclear to cytoplasmic compartments. HSV-1 infection caused similar relocalization phenotypes that required ICP6. However, unlike the infectivity defects previously reported for BORF2-null EBV, ICP6 mutant HSV-1 showed normal growth rates and plaque phenotypes. Combined, these results indicate that both gamma- and alphaherpesviruses use a conserved RNR-dependent mechanism to relocalize A3B and A3A and furthermore suggest that HSV-1 possesses at least one additional mechanism to neutralize these antiviral enzymes.
Identifiants
pubmed: 31534038
pii: JVI.01539-19
doi: 10.1128/JVI.01539-19
pmc: PMC6854502
pii:
doi:
Substances chimiques
Minor Histocompatibility Antigens
0
Proteins
0
Viral Proteins
0
Ribonucleotide Reductases
EC 1.17.4.-
Cytosine Deaminase
EC 3.5.4.1
APOBEC Deaminases
EC 3.5.4.5
APOBEC3 proteins, human
EC 3.5.4.5
APOBEC3A protein, human
EC 3.5.4.5
APOBEC3B protein, human
EC 3.5.4.5
Cytidine Deaminase
EC 3.5.4.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : F30 CA200432
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI083196
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009138
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA234228
Pays : United States
Organisme : CIHR
ID : 153014
Pays : Canada
Organisme : NCI NIH HHS
ID : F31 CA243306
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008244
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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