(C) PLOS One [1]. This unaltered content originally appeared in journals.plosone.org.
Licensed under Creative Commons Attribution (CC BY) license.
url:https://journals.plos.org/plosone/s/licenses-and-copyright

------------



Measles virus exits human airway epithelia within dislodged metabolically active infectious centers

['Camilla E. Hippee', 'Stead Family Department Of Pediatrics', 'Carver College Of Medicine', 'The University Of Iowa', 'Iowa City', 'Iowa', 'United States Of America', 'Brajesh K. Singh', 'Andrew L. Thurman', 'Department Of Internal Medicine']

Date: 2021-09

Measles virus (MeV) is the most contagious human virus. Unlike most respiratory viruses, MeV does not directly infect epithelial cells upon entry in a new host. MeV traverses the epithelium within immune cells that carry it to lymphatic organs where amplification occurs. Infected immune cells then synchronously deliver large amounts of virus to the airways. However, our understanding of MeV replication in airway epithelia is limited. To model it, we use well-differentiated primary cultures of human airway epithelial cells (HAE) from lung donors. In HAE, MeV spreads directly cell-to-cell forming infectious centers that grow for ~3–5 days, are stable for a few days, and then disappear. Transepithelial electrical resistance remains intact during the entire course of HAE infection, thus we hypothesized that MeV infectious centers may dislodge while epithelial function is preserved. After documenting by confocal microscopy that infectious centers progressively detach from HAE, we recovered apical washes and separated cell-associated from cell-free virus by centrifugation. Virus titers were about 10 times higher in the cell-associated fraction than in the supernatant. In dislodged infectious centers, ciliary beating persisted, and apoptotic markers were not readily detected, suggesting that they retain functional metabolism. Cell-associated MeV infected primary human monocyte-derived macrophages, which models the first stage of infection in a new host. Single-cell RNA sequencing identified wound healing, cell growth, and cell differentiation as biological processes relevant for infectious center dislodging. 5-ethynyl-2’-deoxyuridine (EdU) staining located proliferating cells underneath infectious centers. Thus, cells located below infectious centers divide and differentiate to repair the dislodged infected epithelial patch. As an extension of these studies, we postulate that expulsion of infectious centers through coughing and sneezing could contribute to MeV’s strikingly high reproductive number by allowing the virus to survive longer in the environment and by delivering a high infectious dose to the next host.

Measles virus (MeV) is a respiratory pathogen that infects millions worldwide each year. Although sometimes mischaracterized as an innocuous childhood disease, measles remains a leading cause of death for children under five. MeV is the most contagious human virus and requires vaccination rates above 90% to maintain herd immunity. Global decreases in vaccination rates over the past ten years contributed to recent, widespread MeV outbreaks. We uncover here a novel mechanism by which MeV exits the human airways that may explain why it is much more contagious than other viruses. We document that infected cells containing cell-associated virus detach en masse from the airway epithelial sheet. These dislodged infectious centers are metabolically active and can transmit infection to primary human monocyte-derived macrophages via cell-cell contact as efficiently as cell-free virus particles. Thus, cell-associated MeV could spread host-to-host and is a potentially vital strategy for efficient respiratory virus transmission.

In spite of efficient spread between respiratory epithelial cells, viral exit at the apical surface is inefficient: MeV titers in apical washes in vitro and in bronchial alveolar lavages of macaques in vivo are lower than those of other respiratory viruses [ 11 , 21 , 24 , 25 ]. On the other hand, recent studies of MeV spread suggest that cell-associated virus may have a significant role in host-to-host transmission. Specifically, respiratory droplets with the highest viral titers were recovered during intervals when a patient was coughing most frequently [ 26 ]. Throat swabs from experimentally infected macaques revealed cell-associated MeV and the titers of cell-associated and cell-free virus within the swabs were similar [ 25 ].

However, knowledge of the respiratory phase of MeV infection is limited. To model it, we use well-differentiated primary cultures of human airway epithelial cells (HAE) that are maintained at an air-liquid interface. Contrary to initial assumptions, we demonstrated that MeV enters HAE from the basolateral side, delivered by infected immune cells [ 20 , 21 ]. MeV infection of HAE is minimally cytopathic. Epithelial integrity, as monitored by transepithelial electrical resistance, remains intact for weeks after inoculation; in addition, infected cells retain their columnar structure and lateral cytoskeletal interactions without forming visible syncytia [ 22 ]. Using a recombinant MeV expressing green fluorescent protein (GFP), we observed that cytosolic GFP rapidly flows from infected into adjacent cells. These results suggest the formation of pores along the lateral membrane of columnar epithelial cells and provide a route for direct cell-to-cell spread [ 22 ]. Furthermore, using a MeV expressing GFP linked to a component of its ribonucleocapsids (RNP), we observed movement of RNPs along the circumapical F-actin rings of newly infected cells, a strikingly rapid mechanism of horizontal trafficking between epithelial cells [ 23 ].

The MeV replication cycle is fundamentally different from that of other respiratory viruses [ 6 – 8 ]. MeV enters the body through the upper airways and infects alveolar macrophages and dendritic cells that express its primary receptor, the signaling lymphocytic activation molecule (SLAM) [ 9 ]. These cells ferry the infection through the epithelial barrier and spread it to the local lymph nodes [ 10 , 11 ]. Amplification of MeV in immune tissues sets the stage for synchronous, massive invasion of tissues expressing the MeV epithelial receptor, nectin-4 [ 12 – 19 ].

Despite the development of an effective vaccine for measles virus (MeV), measles persists in populations that have limited access to healthcare and is reemerging in populations that refuse vaccinations. MeV outbreaks were extensive in 2019, with 1,282 confirmed cases in the United States and more than 500,000 confirmed cases worldwide [ 1 ]. MeV is of particular concern because of its high transmission potential, measured by the basic reproduction number (R 0 ). MeV has an estimated R 0 value between 12 and 18, which suggests vaccination rates should exceed 92% to protect a community via herd immunity [ 2 – 4 ]. Cases of MeV are projected to rise due to postponed measles vaccination campaigns as healthcare infrastructures focus on COVID-19 cases [ 5 ].

(A) Transepithelial electrical resistance (TER) of MeV-infected HAE (MOI = 1; n = 3) over 21 days of infection. Measured by an epithelial ohm meter with a chopstick electrode (EVOM 2 ; World Precision Instruments) and shown as a percentage of baseline. EdU immunostaining of MeV-infected HAE at (B) 3 days post-infection and (C) 14 days post-infection. EdU was applied for 16 hours at 10 μM before fixation and staining. Images are representative of 4 independent experiments and 9 human donors. Red, EdU; green, MeV-GFP; blue, DAPI; scale bars = 50 μm. (D) The number of infectious centers and EdU+ cells associated with each infectious center were counted. The key shows the number of EdU+ cells associated with an infectious center. The Y-axis signifies the percentage of infectious centers with that number of EdU+ cells for each timepoint. (E) The percentage of cells identified by scRNA-seq over the time course. (F) A schematic describing the quantification of background proliferation is shown. For each HAE culture (mock or MeV-infected), 5 fields of view were imaged at 20x, identified as blue boxes. All EdU+ cells that fell within the field of view were counted unless they were associated with an infectious center, as represented by the counts in the corner of each box. (G) Quantification was performed on HAE infected for 3, 7, 14, or 21 days (MOI = 1; n = 6 human donors as indicated by a unique shape).

After confirming that baseline transepithelial electrical resistance remained constant following MeV-GFP infection of HAE ( Fig 7A ), we asked whether cells situated underneath infectious centers proliferate. To identify dividing cells, we used the DNA synthesis marker 5-ethynyl-2’-deoxyuridine (EdU). Indeed, EdU+ cells were localized with infectious centers ( Fig 7B and 7C ). We then quantified the kinetics of cell division induction below infectious centers. At day 3 post-inoculation, few EdU+ cells were detected in association with infectious centers, but the number of EdU+ cells continuously increased with time ( Fig 7D ). Consistent with this observation, the scRNA-seq dataset indicated an increase of mitotic basal cells over time ( Fig 7E ). A control EdU+ cell count that excluded infectious centers confirmed the quiescent state of cells not located below infectious centers ( Fig 7F and 7G ). These data show that basal cell proliferation is associated with infectious center formation in HAE. Such proliferation may protect the integrity of the epithelium as infectious centers are dislodged from the epithelial sheet.

A gene ontology analysis tool, GenCLiP 2.0, was then used to identify gene expression pathways activated or repressed during infectious center dislodging [ 29 , 30 ]. Interferon and inflammation related pathways were more upregulated in GFP+ cells as compared to GFP- cells ( Fig 6A and 6B ). Of note, apoptosis pathways were downregulated in GFP+ cells ( Fig 6A and 6C ), consistent with our earlier observations ( Fig 3 ). In addition, pathways associated with wound healing, cell growth, and cell differentiation were upregulated in GFP- cells as compared to GFP+ cells ( Fig 6A and 6B ). Cell proliferation genes were upregulated in GFP- cells as compared to GFP+ cells throughout the course of infection ( Fig 6D ). Altogether, these results indicate that apoptotic pathways are inhibited in GFP+ cells as innate immune responses develop. In contrast, GFP- cells begin to differentiate.

To identify enriched or reduced biological processes resulting from MeV infection, we performed unbiased signal pathway analysis. As a comparison between the GFP+, GFP-, and mock groups, lists of differentially expressed genes were generated with a threshold adjusted p-value of 0.05. For GFP+ cells, we identified 91 upregulated genes ( S1 Table ) and 83 downregulated genes ( S2 Table ); for GFP- cells, 66 upregulated genes ( S3 Table ) and 34 downregulated genes ( S4 Table ) were identified.

We also compared the levels of viral RNAs (vRNAs) for each cell type in infected (GFP+ and GFP- combined) and mock-infected cultures over time ( S3D Fig ). Consistent with earlier observations, vRNA was consistently low in non-dividing basal cells. New observations included the existence of increasing vRNA levels in mitotic basal cells, and high levels of vRNA expression in the newly defined interferon-high cluster at 14 days post-infection.

HAE are typically mitotically quiescent. However, we identified two small, but distinct clusters of dividing cells, mitotic basal and mitotic surface. These clusters are primarily composed of both GFP+ and GFP- cells from the day 14 timepoint in infected cultures and are almost absent in mock-infected cells ( Fig 5C and S3A Fig ). Consistent with microscopic evidence showing that basal cells are non-permissive to MeV infection, GFP+ basal cells were uncommon even though they express nectin-4 ( Fig 5D and S4 Fig ). Of note, the cell type specificity of interferon-high cells could not be determined, but these cells were predominately GFP+ ( Fig 5C and 5D ).

Results were visualized in a uniform manifold approximation and projection (UMAP), where cells with similar gene expression profiles cluster ( Fig 5B and 5C , and S3A Fig ). Similar profile distributions were observed for GFP+, GFP-, and mock-infected cells ( Fig 5B and S3B Fig ). Using expression profiles of marker genes ( S3C Fig ), we defined 8 individual clusters ( Fig 5C ), four of them representing the main HAE cell types: secretory, basal, ciliated, and the rare (<1%) pulmonary neuroendocrine cells (PNECs). The four additional clusters were defined by a combination of cell type and phenotypic markers: interferon-high, low unique molecular identifier (UMI), mitotic basal, and mitotic surface.

(A) The experimental design is shown schematically. MeV or mock-infected HAE (n = 10 human donors; MOI = 5) were sorted via FACS at day 3, 7, or 14 post-infection and gated for GFP expression. GFP+ and GFP- cells were collected from MeV-infected HAE. Control cells were sorted via FACS from mock infected cultures (referred to as Mock). Cells from all 10 donors were pooled within their treatment type and prepared for scRNA-seq (10x Genomics). In total, 30,743 cells were sequenced. We projected these cells in a Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) and color-coded them by their treatment group (B) and cell type (C). (D) The percentage of each cell type within each treatment group is shown.

To better understand the cellular response to MeV infection, we performed single-cell RNA-seq (scRNA-seq) on infected HAE cultures at 3, 7, and 14 days post-inoculation, and as control, mock-infected HAE at days 3 and 14 ( Fig 5A ). At the indicated time of infection, HAE were enzymatically dissociated. Single cells were sorted into GFP+ and GFP- groups by fluorescence-activated cell sorting. The percent of recovered GFP+ cells was consistent with microscopy observations, suggesting that infectious centers were successfully dissociated into single cells; however, some loss due to clumping was likely. Each condition included cultures from 10 pooled matched human donors; similar numbers of cells were sequenced and subjected to equally powered bioinformatic analyses. In total, RNAs from 30,743 cells were sequenced via 10x Genomics scRNA-seq.

(A) The experimental design is shown schematically. Monocytes were isolated from human donor blood (n = 2 donors) and treated with selected cytokines to induce differentiation into M2 MDMs. Cell-free and cell-associated virus from MeV-infected HAE (14 days post-infection; n = 3) were applied to the macrophages. (B) Spread was evaluated via inverted fluorescent microscopy two days after transfer to macrophages (scale bars = 50 μm; green arrow, cell-associated virus; red arrow, infected macrophages). Images are representative of 3 independent experiments. (C) The cell-associated and cell-free virus was titered concurrently via TCID 50 . Counts of infected macrophages were adjusted for titer differences. A Student’s t-test indicated no statistical significance. MDM, monocyte-derived macrophages; BF, brightfield.

We next asked if dislodged infectious centers infect macrophages, one of the cell types that ferry virus from the lumen of the airways to the lymphatic organs. To generate macrophages, we isolated monocytes from donated human blood and treated them with the appropriate cytokines to stimulate their differentiation into M2 macrophages ( Fig 4A ). We then co-cultured these M2 macrophages with extruded infectious centers collected from an apical wash of MeV-infected HAE 14 days post-inoculation. As a comparison, we used cell-free virus collected in parallel. Two days later, macrophages were examined for signs of infection using microscopy ( Fig 4B ). Cell-associated virus (green arrow) spread MeV to nearby macrophages (red arrows); cell-free MeV also infected macrophages, but its lower titers limited the effective MOI. Because infection of macrophages was performed on the same day as the wash collection from the HAEs, the input titer could not be determined at the time of infection. Thus, the quantity of virus added to the macrophages was determined post-hoc. When the number of infected macrophages were quantified by visual counting and normalized to account for input titer differences, we observed similar levels of infectivity between cell-associated and cell-free MeV ( Fig 4C ). These experiments suggest that when normalized to input PFU, infectious centers are as effective as cell-free virus in delivering MeV to macrophages. However, since most virus remains cell-associated, dislodged infectious centers may be the primary infection spreader. We next sought to better understand the mechanism of infectious center dislodging from the epithelial sheet.

(A) Apical washes were collected from MeV-infected HAE (14 days post-infection; MOI = 1), fixed, and immunostained for cleaved caspase-3 (CASP3). (B) HAE were treated with staurosporine (100 μM, 5 hrs) as a positive control to induce apoptosis, fixed, and immunostained for CASP3 (red), DAPI (blue), and phalloidin (gray). Scale bar = 50μm. (C) Western blot was performed on lysates from mock or MeV-infected HAE (n = 3; MOI = 1). Blots were probed for cleaved CASP3 and MeV N-protein. α-tubulin was used as a loading control protein. Staurosporine (stauro) treatment was used as a positive control. (D) Caspase-3 activity was assayed following mock, staurosporine (100 μM, 5 hrs), MeV (MOI = 1), or respiratory syncytial virus (RSV, MOI = 1) treatment of HAE (14 days post-infection; n = 3 human donors with 2 technical replicates). Fluorescence was measured in arbitrary units (AU) via plate reader. ****p < 0.0001; *p < 0.05.

To assess the extent to which viability is preserved in dislodged infectious centers, we used immunostaining to measure cleaved caspase-3, an apoptosis marker. Dislodged infectious centers were negative for caspase-3 staining ( Fig 3A ); whereas, HAE treated with a positive control, protein kinase inhibitor staurosporine, were caspase-3 positive ( Fig 3B ). Western blotting confirmed that cleaved caspase-3 is not found in the lysates of mock or MeV-infected HAE over 14 days ( Fig 3C ). As an additional control, we used respiratory syncytial virus (RSV), a pneumovirus that induces apoptosis and apical cell dislodging in the bronchus of infants [ 28 ]. Caspase-3 and caspase-7 activity was significantly higher in RSV-infected HAE than in mock-infected HAE ( Fig 3D ), but these activities remained at background level in MeV-infected HAE. In addition, cells collected from apical washes of MeV-infected HAE remained viable as determined by an ATP-based viability assay ( S2A Fig ). Mock and MeV-infected HAE showed similar metabolic activity ( S2A and S2B Fig ). Altogether, these results indicate that the cells within MeV infectious centers remain viable after dislodging from the epithelial sheet.

(A) Basolateral media, cell lysates, and apical washes were collected from HAE at 3, 7, 10, 14, 18, and 21 days post-infection (MOI = 1). Apical washes were gently centrifuged to separate cell-free virus from cell-associated virus. (B) TCID 50 titers were performed on all four sample types at each timepoint (n = 3 human donors). Means ± standard deviations are shown on a log scale. The limit of detection (200 TCID 50 /mL) is set as the minimum on the Y-axis. ND = not detected. *p<0.05, cell-free vs. cell-associated. (C) Apical washes were mounted on coverslips and dislodged infectious centers were counterstained with DAPI (blue) and phalloidin (red). Images were collected with confocal microscopy and are representative of 3 human donors.

To investigate the relevance of infectious center dislodging for virus transmission, we sought to quantify virus load in infected HAE cultures. We collected apical washes, cell lysates, and basolateral media from infected HAE every 3–4 days for 21 days post-infection. Apical washes were gently centrifuged in order to separate cell-free virus in the supernatant from cell-associated virus in the pellet ( Fig 2A ). We then measured virus titer in cell lysates, basolateral media, and cell-free and cell-associated virus from apical media ( Fig 2B ). High titers were observed in the cell lysates starting at 7 days post-inoculation, consistent with microscopy observations. In apical washes, virus titers were very low through day 10 post-inoculation. Starting from day 14, cell-associated virus titers were at least 10-fold higher than cell-free virus titers. These results indicate that most infectious MeV remains cell associated and exits the epithelial sheet via cell dislodging.

(A) Live fluorescence microscopy of HAE infected with MeV-GFP (MOI = 1) over a time course of 21 days. All images are from the same field of view and are representative of 3 human donors. Colored arrows indicate examples of unique infectious centers that disappear during the time course. Scale bars = 500 μm. (B and C) En face and vertical confocal images of infectious centers at 3 days post-infection and 21 days post-infection, respectively. Z-stack images from B and C were used to create 3D models (D and E) respectively. Green, MeV-GFP; blue, DAPI.

Using a MeV (wild-type IC-323 strain) that expresses green fluorescent protein (MeV-GFP), we infected HAE (MOI = 1) from the basolateral surface and live-imaged infectious centers at low power over a period of 3 weeks ( Fig 1A ). During the first ~5 days of infection, MeV spreads to surrounding cells, causing the infectious centers to grow in size. Around 7–10 days post-infection, infectious centers often “disappear” from the epithelial sheet. To understand their fate, we performed confocal microscopy at an early time point, day 3 ( Fig 1B and S1 Movie ), and a late time point, day 21 ( Fig 1C and S2 Movie ). In contrast to day 3, at day 21 the infectious center was dislodging from the epithelial layer. The cells of the infectious center remained clustered while detaching from uninfected epithelia, causing the infectious center to shed as a unit, as shown in the 3D reconstruction models ( Fig 1D and 1E and S1 Fig ).

Discussion

We demonstrate that MeV exits HAE within dislodged infectious centers. We also show that dislodged infectious centers can transmit infection to human macrophages, one of the cell types that carries infectivity from the lumen of a new host’s airways to its lymphatic organs. Since dislodged infectious centers contain the most released virus, they may have a central role in host-to-host transmission. Our results also indicate that little cell-free virus is released from HAE, which challenges the idea that apical budding is the major pathway by which MeV exits the airways, and affirms the idea that cell-associated virus is a significant contributor to transmission [31–34].

Infectious center dislodging is consistent with published in vivo observations. The presence of exfoliated giant epithelial cells in swab samples from patients is a diagnostic feature of measles [35,36]. Giant cells can be detected in nasopharyngeal mucus from the start of the measles rash, and the duration of their excretion correlates with severity of acute disease [36]. In bronchial alveolar lavages from experimentally infected macaques, Ludlow et al. documented high numbers of MeV-infected cells or cell debris “spilling” from epithelia into the respiratory tract [25]. These authors also measured equivalent titers of expelled cell-free and cell-associated virus released into the airways and attributed the presence of cells in the airways to stimulation of the cough response. Infectious centers peel away from the epithelial sheet without physical intervention, suggesting that coughing is not required to dislodge infected cells. Consistent with in vivo observations [25], infectious center dislodging may promote coughing and sneezing that contributes to the infectious nature of MeV. Following infectious center dislodging, the cells could potentially separate into single cells; however, our observations of apical washings suggest that the cell groupings remain intact. Although the primary spread of MeV appears to be through aerosols and respiratory droplets, fomites coated with dislodged infectious centers could also be a significant contributor in viral transmission [17,26,37,38]. The high transmissibility of MeV is likely due to exploitation of multiple transmission routes in parallel: fomites, droplets, and long-distance airborne transmission by aerosols.

MeV is the most contagious human virus [2–4]. However, the limited currently available transmission studies do not explain why MeV is so much more transmissible than other respiratory viruses. We think that metabolically active MeV infectious centers could survive in the environment longer than viral particles, and that dislodging of infectious centers accounts in part for the MeV’s high basic reproduction number. Infectious center-based spread is another example of increased viral transmission achieved through packaging and co-transmission of multiple genomes. Other examples of packaging include the encapsulation of enteroviruses in vesicles, and baculovirus ocular bodies that are more resistant to heat, desiccation, radiation, and chlorine treatment when compared to free virus [39–41]. Vesicle-cloaked rotaviruses are more infectious than free virions, and it is postulated that virions enclosed in vesicles are protected from degradation by intestinal proteases and/or bile acids [41]. Enteric hepatitis A virus (HAV) membrane-encapsulated virions provide protection against neutralizing antibodies that result in enhanced spread within a host [42]. Another advantage of virus delivery through infectious centers is high titer “en bloc” transmission of multiple genomes [43,44]. As such, the combination of cell-free and cell-associated MeV spread could result in a two pronged attack: a long-distance airborne aerosol transmission and an environmentally stable infectious center. Further experiments are required to confirm the survival benefits of MeV remaining cell-associated in the environment.

While apoptosis is detected in primary epithelial cells infected with other respiratory viruses [28,45,46], our scRNA-seq data, lack of detection of activated caspases, and the documentation of ciliary beating in dislodged infectious centers indicate that MeV can effectively control apoptosis of well-differentiated HAE. Cell viability assays performed on washings from infected HAE support this observation. Based on insights from gene ontology analyses, future studies will focus on genes controlling wound healing pathways and cell adhesion processes as potential regulators of the dislodging mechanisms.

The host response may promote the dislodging of infectious centers that pose a risk to the integrity to the epithelial sheet. Indeed, live cell extrusion from epithelial sheets can result from multiple stimuli, such as overcrowding, tumor suppression, or invasion by pathogens [47–50]. Our results show that basal cell proliferation occurs directly underneath infectious centers. Cell proliferation may reflect the host’s response to replace dislodging or damaged cells, promoting extrusion by “pushing” infectious centers off the epithelial layer. We observed by microscopy, and confirmed though scRNA-seq, that basal cells are rarely infected by MeV. Since basal cells are the primary proliferative cell type in differentiated epithelia, this could explain how the epithelia can maintain integrity for at least 21 days. The relatively low expression of nectin-4, the epithelial cellular receptor for MeV [18,19], in basal cells could account, in part, for their non-permissiveness to MeV infection; however, additional studies are required to determine how basal cells are resistant to MeV.

We acknowledge that this study has limitations. First, all experiments were performed in vitro. Unpassaged primary HAE cultures recapitulate the in vivo airway surface epithelium in cell type distribution and morphology. However, they do not contain immune cells which contribute to clearing infections from the airways and may impact infectious center growth and/or dislodging. Indeed, the detection of cell free virus titers in measles infected patients [51] could potentially be explained by contribution of MeV produced by immune cells in the upper respiratory tract [25]. Second, the single cell sequencing experiments necessitated sorting to enrich for MeV infected (ie, GFP+) cells and ensure adequate sampling. As a result, we are aware that cell sorting may have skewed our samples toward cell types that are more easily disassociated into single cell populations, potentially excluding cells from infectious centers. Finally, experiments with HAE do not allow us to test the efficacy or in vivo time course of host-to-host spread of cell-associated MeV. To address these limitations, future research should include in vivo non-human primate studies or perhaps a proxy such as canine distemper virus in ferrets.

In summary, our results document that MeV uses a novel mechanism of infectious center dislodging to exit airway epithelia. Cell-associated MeV in dislodged infectious centers may be protected from environmental stressors that promote virion degradation during inter-host transmission. Active expulsion of infectious centers into the environment may contribute to the exceptionally high transmission efficiency of MeV.

[END]

[1] Url: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009458

(C) Plos One. "Accelerating the publication of peer-reviewed science."
Licensed under Creative Commons Attribution (CC BY 4.0)
URL: https://creativecommons.org/licenses/by/4.0/


via Magical.Fish Gopher News Feeds:
gopher://magical.fish/1/feeds/news/plosone/

You are viewing proxied material from magical.fish. The copyright of proxied material belongs to its original authors. Any comments or complaints in relation to proxied material should be directed to the original authors of the content concerned. Please see the disclaimer for more details.