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In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit
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 M...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for General Microbiology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167896/ https://www.ncbi.nlm.nih.gov/pubmed/21471322 http://dx.doi.org/10.1099/vir.0.031542-0 |
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author | Milho, Ricardo Gill, Michael B. May, Janet S. Colaco, Susanna Stevenson, Philip G. |
author_facet | Milho, Ricardo Gill, Michael B. May, Janet S. Colaco, Susanna Stevenson, Philip G. |
author_sort | Milho, Ricardo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3167896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Society for General Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-31678962011-10-03 In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit Milho, Ricardo Gill, Michael B. May, Janet S. Colaco, Susanna Stevenson, Philip G. J Gen Virol Animal 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. Society for General Microbiology 2011-07 /pmc/articles/PMC3167896/ /pubmed/21471322 http://dx.doi.org/10.1099/vir.0.031542-0 Text en © 2011 SGM http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Animal Milho, Ricardo Gill, Michael B. May, Janet S. Colaco, Susanna Stevenson, Philip G. In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title | In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title_full | In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title_fullStr | In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title_full_unstemmed | In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title_short | In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
title_sort | in vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit |
topic | Animal |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167896/ https://www.ncbi.nlm.nih.gov/pubmed/21471322 http://dx.doi.org/10.1099/vir.0.031542-0 |
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