Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells

Ludlow, Martin; Lemon, Ken; Vries, Rory D. de; McQuaid, Stephen; El, Millar; G, van Amerongen; Yüksel, Selma; Rj, Verburgh; Osterhaus, Albert D. M. E.; Swart, Rik L. de; Duprex, W. Paul

doi:10.1128/jvi.03258-12

Cited by 60 publications

(69 citation statements)

References 24 publications

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“…In summary, we propose that MV infection of adenoid and tonsillar lymphoid tissue with subsequent epithelial damage in the URT contributes to the emergence of transmissible virus in the respiratory tract, augmenting previously proposed sources such as MV-infected epithelial cells in the trachea (Mühlebach et al, 2011) and nose (Ludlow et al, 2013). Future studies focused on aerosolized transmission of fluorescent morbilliviruses in the ferret, a model used extensively for virus transmission studies (Herfst et al, 2012;Imai et al, 2012), would help to illuminate natural routes of virus transmission and provide the basis for more challenging studies into natural transmission of MV in the macaque.…”

Section: Discussionmentioning

confidence: 99%

“…Between 9 and 11 days p.i. we also observed widespread infection of epithelial tissues in the nose (Ludlow et al, 2013). In order to assess whether virus infection in the upper respiratory tract (URT) of macaques was associated with virus shedding we examined the release of virus into the airways between 0 and 13 days p.i.…”

Section: Resultsmentioning

confidence: 99%

“…Animals were euthanized by exsanguination under ketamine/medetomidine anaesthesia, macroscopic foci containing EGFP were visualized and imaged, and samples collected for histological, immunohistochemical or immunocytochemical analysis as described previously (de Swart et al, 2007;de Vries et al, 2010a;Ludlow et al, 2013). Representative areas from lung, trachea, primary bronchus, tonsil, adenoid, nasal concha, tongue, buccal mucosa and inner cheek were sampled.…”

Section: Methodsmentioning

confidence: 99%

“…These MV-infected immune cells contacting or infiltrating into respiratory epithelium spread infection to PVRL4 + epithelial cells in the late stages of the disease (Frenzke et al, 2013;Ludlow et al, 2013). Macaques provide an excellent natural model in which to investigate the late stages of measles as a number of outbreaks have been reported in primate colonies with extensive chains of transmission between animals (Choi et al, 1999;MacArthur et al, 1979;Willy et al, 1999).…”

Section: Measles Virus (Mv) a Morbillivirus In The Familymentioning

confidence: 99%

“…The identification of CD150 as the primary MV cellular receptor on activated B-and Tlymphocytes, macrophages and mature dendritic cells (Tatsuo et al, 2000) explains the largely lymphotropic nature of measles. The more recent discovery that PVRL4 (Nectin 4), a component of the adherens junction, is also a bona fide MV cellular receptor (Mühlebach et al, 2011;Noyce et al, 2011) explains the epitheliotropism observed in the late stages of the disease (Ludlow et al, 2010(Ludlow et al, , 2013.…”

Section: Measles Virus (Mv) a Morbillivirus In The Familymentioning

confidence: 99%

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Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

Ludlow

Vries

Lemon

et al. 2013

Journal of General Virology

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Measles virus (MV), a member of the family Paramyxoviridae, remains a major cause of morbidity and mortality in the developing world. MV is spread by aerosols but the mechanism(s) responsible for the high transmissibility of MV are largely unknown. We previously infected macaques with enhanced green fluorescent protein-expressing recombinant MV and euthanized them at a range of time points. In this study a comprehensive pathological analysis has been performed of tissues from the respiratory tract around the peak of virus replication. Isolation of virus from nose and throat swab samples showed that high levels of both cell-associated and cell-free virus were present in the upper respiratory tract. Analysis of tissue sections from lung and primary bronchus revealed localized infection of epithelial cells, concomitant infiltration of MV-infected immune cells into the epithelium and localized shedding of cells or cell debris into the lumen. While high numbers of MV-infected cells were present in the tongue, these were largely encapsulated by intact keratinocyte cell layers that likely limit virus transmission. In contrast, the integrity of tonsillar and adenoidal epithelia was disrupted with high numbers of MV-infected epithelial cells and infiltrating immune cells present throughout epithelial cell layers. Disruption was associated with large numbers of MV-infected cells or cell debris 'spilling' from epithelia into the respiratory tract. The coughing and sneezing response induced by disruption of the ciliated epithelium, leading to the expulsion of MV-infected cells, cell debris and cell-free virus, contributes to the highly infectious nature of MV.

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Measles Virus (Mv) a Morbillivirus In The Familymentioning

confidence: 99%

Section: Measles Virus (Mv) a Morbillivirus In The Familymentioning

confidence: 99%

See 3 more Smart Citations

Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

Ludlow

Vries

Lemon

et al. 2013

Journal of General Virology

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High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system

Grein

Loewe

Dieken

et al. 2018

Biotech & Bioengineering

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Oncolytic viruses offer new hope to millions of patients with incurable cancer. One promising class of oncolytic viruses is Measles virus, but its broad administration to cancer patients is currently hampered by the inability to produce the large amounts of virus needed for treatment (10 -10 virus particles per dose). Measles virus is unstable, leading to very low virus titers during production. The time of infection and time of harvest are therefore critical parameters in a Measles virus production process, and their optimization requires an accurate online monitoring system. We integrated a probe based on dielectric spectroscopy (DS) into a stirred tank reactor to characterize the Measles virus production process in adherent growing Vero cells. We found that DS could be used to monitor cell adhesion on the microcarrier and that the optimal virus harvest time correlated with the global maximum permittivity signal. In 16 independent bioreactor runs, the maximum Measles virus titer was achieved approximately 40 hr after the permittivity maximum. Compared to an uncontrolled Measles virus production process, the integration of DS increased the maximum virus concentration by more than three orders of magnitude. This was sufficient to achieve an active Measles virus concentration of > 10 TCID ml .

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Impact of Bioreactor Geometry on Mesenchymal Stem Cell Production in Stirred‐Tank Bioreactors

Petry

Salzig

2021

Chemie Ingenieur Technik

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Human mesenchymal stem cells (hMSCs) are manufactured as cell therapy products. This requires a tightly controlled and fully understood production process, usually taking place in a stirred‐tank bioreactor. In this review, the impact of bioreactor geometry as well as equipment‐related parameters is discussed. We provide a theoretical background for the engineering of hMSC spheroids with a defined size and evaluate the process parameters needed for the microcarrier‐based expansion of hMSCs. Finally, and based on experimental data, ideal bioreactor setups for each type of process are recommended.

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Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells

Cited by 60 publications

References 24 publications

Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system

Impact of Bioreactor Geometry on Mesenchymal Stem Cell Production in Stirred‐Tank Bioreactors

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