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Alveolar Macrophages Are a Prominent but Nonessential Target for Murine Cytomegalovirus Infecting the Lungs

Overview of attention for article published in Journal of Virology, December 2015
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Title
Alveolar Macrophages Are a Prominent but Nonessential Target for Murine Cytomegalovirus Infecting the Lungs
Published in
Journal of Virology, December 2015
DOI 10.1128/jvi.02856-15
Pubmed ID
Authors

Helen E. Farrell, Clara Lawler, Martha T. Oliveira, Nick Davis-Poynter, Philip G. Stevenson

Abstract

Cytomegaloviruses (CMVs) infect the lungs and cause pathological damage there in immunocompromised hosts. How lung infection starts is unknown. Inhaled murine CMV (MCMV) directly infected alveolar macrophages (AMs) and type 2 alveolar epithelial cells (AEC2s), but not type 1 AECs (AEC1s). By contrast Herpes simplex virus type 1 infected AEC1s, and Murid Herpesvirus-4 (MuHV-4) infected AEC1s via AMs. MCMV-infected AMs prominently expressed viral reporter genes from an HCMV IE1 promoter; but most IE1(+) cells were AEC2s, and CD11c-cre mice, which express cre in AMs, switched <5% of floxed MCMV in the lungs. By contrast they switched >90% of floxed MuHV-4 in the lungs and 50% of floxed MCMV in the blood. AM depletion also increased acute MCMV lung titers. Thus, their influence was more restrictive than permissive. Circulating monocytes entered infected lungs in large numbers and became infected, but not directly - this occurred mainly via AEC2s. MCMV lacking its m131/m129 chemokine homolog, which promotes macrophage infection, showed a modest difference in lung infiltration by Gr-1(+) cells and no defect in lung infection. These results were consistent with myeloid cells mainly disseminating MCMV from the lungs, whereas AEC2s provided local amplification. Cytomegaloviruses (CMVs) chronically and systemically infect most mammals. Human CMV infection is usually asymptomatic, but causes lung disease in people with poor immune function. As human infection is hard to analyse, related animal viruses provide important insights. We show that Murine CMV has two targets in the lungs: macrophages and surfactant-secreting epithelial cells. Acute virus replication occurred largely in the epithelial cells. Macrophages had an important defensive role, as removing them increased infection. These results establish the dual nature of lung infection, with local virus replication in epithelial cells, and spread via quiescently infected macrophages. Distinct therapies may be needed to target these contrasting events.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 29%
Researcher 3 18%
Unspecified 3 18%
Professor 2 12%
Student > Master 1 6%
Other 3 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 29%
Immunology and Microbiology 5 29%
Unspecified 3 18%
Medicine and Dentistry 2 12%
Environmental Science 1 6%
Other 1 6%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 January 2016.
All research outputs
#10,982,391
of 12,359,087 outputs
Outputs from Journal of Virology
#12,133
of 13,153 outputs
Outputs of similar age
#278,086
of 338,753 outputs
Outputs of similar age from Journal of Virology
#240
of 272 outputs
Altmetric has tracked 12,359,087 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,153 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 338,753 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 272 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.