Lymph node macrophages restrict murine cytomegalovirus dissemination

Farrell, Helen E., Davis-Poynter, Nick, Bruce, Kimberley, Lawler, Clara, Dolken, Lars, Mach, Michael and Stevenson, Philip G. (2015) Lymph node macrophages restrict murine cytomegalovirus dissemination. Journal of Virology, 89 14: 7147-7158. doi:10.1128/JVI.00480-15

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ360090_OA.pdf Full text (open access) application/pdf 4.86MB 0

Author Farrell, Helen E.
Davis-Poynter, Nick
Bruce, Kimberley
Lawler, Clara
Dolken, Lars
Mach, Michael
Stevenson, Philip G.
Title Lymph node macrophages restrict murine cytomegalovirus dissemination
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2015-07
Year available 2015
Sub-type Article (original research)
DOI 10.1128/JVI.00480-15
Open Access Status File (Publisher version)
Volume 89
Issue 14
Start page 7147
End page 7158
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2016
Language eng
Formatted abstract
Cytomegaloviruses (CMVs) establish chronic infections that spread from a primary entry site to secondary vascular sites such as the spleen, then to tertiary shedding sites such as the salivary glands. Human CMV (HCMV) is difficult to analyze because its spread precedes clinical presentation. Murine CMV (MCMV) offers a tractable model. It is hypothesized to spread from peripheral sites via vascular endothelial cells and associated monocytes. However viral luciferase imaging showed footpad-inoculated MCMV reaching first the popliteal lymph nodes (PLN). PLN colonization was rapid and further spread was slow, implying that LN infection can be a significant bottleneck. Most acutely infected PLN cells were CD169+ subcapsular sinus macrophages (SSM). Replication-deficient MCMV also reached them, indicating direct infection. Many SSM expressed viral reporter genes but few expressed lytic genes; SSM expressed CD11c, and MCMV with a cre-sensitive fluorochrome switch showed switched infected cells in PLN of CD11c-cre mice, but yielded little switched virus; and SSM depletion with liposomal clodronate or via a CD169-diphtheria toxin receptor transgene shifted infection to ER-TR7+ stromal cells, increased virus production and accelerated its spread to the spleen. Therefore MCMV disseminated via LN, and SSM slowed this spread by shielding permissive fibroblasts and supporting poorly viral lytic replication.

Importance Human cytomegalovirus (HCMV) chronically infects most people, causing congenital disability and harming the immunocompromised. A major goal of vaccination is to prevent systemic infection. How this is established is unclear. Restriction to humans makes HCMV difficult to analyse. We show that peripheral Murine CMV (MCMV) infection spreads via lymph nodes. Here MCMV infected filtering macrophages, which supported virus replication poorly. When these macrophages were depleted, MCMV infected susceptible fibroblasts and spread faster. The capacity of filtering macrophages to limit MCMV spread argued that their infection is an important bottleneck in host colonization, and so might be a good a vaccine target.

Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
Child Health Research Centre Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 15 May 2015, 10:02:07 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences