In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit.
J Gen Virol
; 92(Pt 7): 1550-1560, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21471322
ABSTRACT
The difficulty of eliminating herpesvirus carriage makes host entry a key target for infection control. However, its viral requirements are poorly defined. Murid herpesvirus-4 (MuHV-4) can potentially provide insights into gammaherpesvirus host entry. Upper respiratory tract infection requires the MuHV-4 thymidine kinase (TK) and ribonucleotide reductase large subunit (RNR-L), suggesting a need for increased nucleotide production. However, both TK and RNR-L are likely to be multifunctional. We therefore tested further the importance of nucleotide production by disrupting the MuHV-4 ribonucleotide reductase small subunit (RNR-S). This caused a similar attenuation to RNR-L disruption despite reduced intra-host spread, invasive inoculations still established infection, whereas a non-invasive upper respiratory tract inoculation did so only at high dose. Histological analysis showed that RNR-S(-), RNR-L(-) and TK(-) viruses all infected cells in the olfactory neuroepithelium but unlike wild-type virus then failed to spread. Thus captured host nucleotide metabolism enzymes, up to now defined mainly as important for alphaherpesvirus reactivation in neurons, also have a key role in gammaherpesvirus host entry. This seemed to reflect a requirement for lytic replication to occur in a terminally differentiated cell before a viable pool of latent genomes could be established.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleotídeo Redutases
/
Proteínas Virais
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Rhadinovirus
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Gen Virol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido