Epithelial giant cells in measles as an aid in diagnosis

Lightwood, Reginald; Nolan, Regina; Franco, Marino G. Di; White, Anthony J.

doi:10.1016/s0022-3476(70)80045-2

Cited by 41 publications

(23 citation statements)

References 17 publications

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“…This is supported by the fact that the release of giant cells into the lumen of the respiratory tract is a consistent pathological feature of measles (Mcquillin et al, 1976;Scheifele & Forbes, 1972;Tompkins & Macaulay, 1955). Such cells obtained from nasopharyngeal or conjunctival swabs can be detected during the prodromal stage and have proven invaluable as an additional diagnostic feature of measles in resource-limited areas (Lightwood et al, 1970). Similarly, we also detected MVinfected cells and associated subcellular debris in the lumen of the respiratory tract together with cell-associated virus in nose and throat swabs taken from infected macaques.…”

Section: Discussionmentioning

confidence: 96%

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: 96%

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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“…However, we found that the tight junction protein ZO-1 was present at the membranes of in vitro and in vivo MV-infected epithelial cells, suggesting that, at least in small foci of infection, the epithelial barrier remains intact and that virus spreads between cells without the breakdown of cell membranes, similar to the spread of wild-type MV in endothelial cell monolayers (Andres et al, 2003). Thus, exfoliated epithelial giant cells in swab samples taken from patients -a historical diagnostic feature of measles (Lightwood & Nolan, 1970;Scheifele & Forbes, 1972) -may not arise as a consequence of direct MV infection but instead may occur as result of an inflammatory immune response. Interestingly, similar epithelial giant cells are often reported in cases of non-specific chronic inflammation of the nasopharynx (Ali, 1965).…”

Section: Discussionmentioning

confidence: 99%

“…This study also emphasized the importance of MV spread and dissemination within the body through cell-to-cell contact rather than through the development of large multinucleated syncytia in which only a minority of the MVinfected cells present in lymphoid tissues were observed to reside. Many studies have reported extensive epithelial cell infection during measles (Kimura et al, 1975;Lightwood & Nolan, 1970; Moench et al, 1988;Olding-Stenkvist & Bjorvatn, 1976). However, in the absence of appropriate epithelial and immune cell markers, caution should be applied in using such studies to support a prominent role for epithelial cells in the pathogenesis of measles.…”

Section: Introductionmentioning

confidence: 99%

Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus

Ludlow

Rennick

Sarlang

et al. 2009

Journal of General Virology

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The lymphotropic and myelotropic nature of wild-type measles virus (wt-MV) is well recognized, with dendritic cells and lymphocytes expressing the MV receptor CD150 mediating systemic spread of the virus. Infection of respiratory epithelial cells has long been considered crucial for entry of MV into the body. However, the lack of detectable CD150 on these cells raises the issue of their importance in the pathogenesis of measles. This study utilized a combination of in vitro, ex vivo and in vivo model systems to characterize the susceptibility of epithelial cells to wt-MV of proven pathogenicity. Low numbers of MV-infected epithelial cells in close proximity to underlying infected lymphocytes or myeloid cells suggested infection via the basolateral side of the epithelium in the macaque model. In primary cultures of human bronchial epithelial cells, foci of MV-infected cells were only observed following infection via the basolateral cell surface. The extent of infection in primary cells was enhanced both in vitro and in ex vivo cornea rim tissue by disrupting the integrity of the cells prior to the application of virus. This demonstrated that, whilst epithelial cells may not be the primary target cells for wt-MV, areas of epithelium in which tight junctions are disrupted can become infected using high m.o.i. The low numbers of MV-infected epithelial cells observed in vivo in conjunction with the absence of infectious virus release from infected primary cell cultures suggest that epithelial cells have a peripheral role in MV transmission. INTRODUCTIONMeasles is a severe disease contributing to significant morbidity and mortality rates in many parts of the developing world (Grais et al., 2007). It is also of growing concern in some areas of the developed world where the vaccination rate has fallen below the level required to prevent periodic outbreaks of measles (Choi et al., 2008). The disease is characterized by fever and a maculopapular rash, often in conjunction with cough, coryza and/or conjunctivitis, and a generalized immunosuppression. The causative agent, wild-type measles virus (wt-MV) is spread by aerosolized droplets or direct contact (Griffin, 2007). The highly infectious nature of MV not only suggests a very efficient route of entry into the body but also an effective means of dissemination to susceptible individuals following systemic spread of the virus within the body.The tropism of MV in vivo is determined mainly by the distribution of CD150, also known as signalling lymphocyte activation molecule (SLAM), which is the primary cellular receptor for wild-type strains of the virus. The molecule is widely expressed in lymphoid tissues on subsets of B and T lymphocytes, thymocytes, macrophages and dendritic cells (DCs) (Kruse et al., 2001;McQuaid & Cosby, 2002). This is reflected by analysis of MV-infected cell types present at different stages of the disease, which shows that, in all tissues involved, the majority of infected cells are of a lymphoid origin (Hall et al., 1971; Moench et al., 1988). Ano...

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“…3A) and also in humans (23 sles, such as coughing, Koplik spots, and maculopapular rashes (14,17), developed in one of the monkeys as reported for IC-B-infected monkeys (16). Histopathological examinations on the monkeys autopsied on day 11 demonstrated extensive giant cell formation of lymphoid cells called WarthinFinkeldey cells (19) as well as a number of MeV-infected mononuclear cells, which were stained intensively by the immunoperoxidase method using anti-MeV N monoclonal antibody, in lymphoid organs (data not shown). Giant cells were also found in the bronchiolar cells, epidermal cells of oral mucosa with mild acanthosis and intraepidermal neutrophil infiltration, and epidermis and hair follicles around skin rashes.…”

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confidence: 95%