Rapid Detection of Measles Virus III Skin Rashes by Immunofluorescence

Olding-Stenkvist, Elisabeth; Bjorvatn, Bjarne

doi:10.1093/infdis/134.5.463

Cited by 42 publications

(15 citation statements)

References 10 publications

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“…At that time, only SLAM/CD150-positive cells were found to be susceptible to wt MV infections. However, it remained difficult to make a final conclusion that SLAM/CD150 is the sole receptor for wt MV, because histopathological examinations of measles patients and monkeys infected with MV have revealed considerable levels of MV protein expression in the epithelia of various organs, and histopathological changes are also evident in these epithelia (Nii et al, 1964; Lightwood and Nolan, 1970; Olding-Stenkvist and Bjorvatn, 1976; Moench et al, 1988; Craighead, 2000; Figure 1). In 2003, primary cultures of human small airway epithelial cells (SAECs) were shown to be susceptible to wt MV infection (Takeuchi et al, 2003).…”

Section: Discoveries Of Cellular Receptors For MVmentioning

confidence: 99%

Wild-Type Measles Virus is Intrinsically Dual-Tropic

Takeda¹,

Tahara²,

Nagata³

et al. 2012

Front. Microbio.

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Measles is a highly contagious disease that causes temporary and severe immunosuppression in patients. Signaling lymphocyte activation molecule (SLAM) expressed on cells of the immune system functions as a receptor for measles virus (MV). In addition to SLAM, vaccine strains of MV also use a ubiquitously expressed complement regulatory protein, CD46, as a receptor, whereas wild-type (wt) MV strains do not use this receptor. However, recent studies have indicated that SLAM is not the sole receptor for wt MV strains. These strains have an intrinsic ability to enter both immune and epithelial cells using distinct receptor binding sites in their hemagglutinin (H) protein. Recently, a clear answer was obtained through the identification of an epithelial MV receptor, nectin4, expressed at adherens junctions, thereby greatly improving our knowledge of MV receptors. It is now clear that MV specifically targets two cell types, immune cells and epithelial cells, using SLAM and nectin4, respectively. MV loses the ability to use either SLAM or nectin4 when it possesses specific mutations in the H protein. However, nectin4-blind MV still infects SLAM-positive immune cells efficiently (SLAM-tropic), and conversely, SLAM-blind MV infects nectin4-positive epithelial cells efficiently (nectin4-tropic). In this regard, MV is intrinsically dual-tropic to immune cells and epithelial cells. Although many aspects and molecular mechanisms underlying immunosuppressive effects and a highly contagious nature of MV still remain to be elucidated, analyses of physiological functions of these two receptors would provide deep insights into MV pathogenesis.

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Section: Discoveries Of Cellular Receptors For MVmentioning

confidence: 99%

Wild-Type Measles Virus is Intrinsically Dual-Tropic

Takeda¹,

Tahara²,

Nagata³

et al. 2012

Front. Microbio.

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“…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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“…Although CD46, a ubiquitously expressed complement regulatory molecule, functions as a receptor for the vaccine strains of MV (8, 30), a great majority of viruses circulating in measles patients use SLAM, but not CD46, as a receptor (35,51). A recent study of MV infection in macaque monkeys also identified SLAM ϩ lymphocytes and dendritic cells as the predominantly infected cell types (6).However, pathological data from humans and experimentally infected monkeys have shown that MV antigens and syncytia are also detected in epithelial tissues in various organs, such as the skin, oral mucosa, pharynx, trachea, esophagus, intestines, and urinary bladder (5,24,26,27,31,33,34,37). Epithelial cells do not express SLAM, and wild-type (WT) strains of MV, unlike vaccine strains, do not infect epithelial cell lines.…”

mentioning

confidence: 99%

“…However, pathological data from humans and experimentally infected monkeys have shown that MV antigens and syncytia are also detected in epithelial tissues in various organs, such as the skin, oral mucosa, pharynx, trachea, esophagus, intestines, and urinary bladder (5,24,26,27,31,33,34,37). Epithelial cells do not express SLAM, and wild-type (WT) strains of MV, unlike vaccine strains, do not infect epithelial cell lines.…”

mentioning

confidence: 99%

Measles Virus Infects both Polarized Epithelial and Immune Cells by Using Distinctive Receptor-Binding Sites on Its Hemagglutinin

Tahara

Takeda

Shirogane

et al. 2008

J Virol

105

108

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Measles is one of the most contagious human infectious diseases and remains a major cause of childhood morbidity and mortality worldwide. The signaling lymphocyte activation molecule (SLAM), also called CD150, is a cellular receptor for measles virus (MV), presumably accounting for its tropism for immune cells and its immunosuppressive properties. On the other hand, pathological studies have shown that MV also infects epithelial cells at a later stage of infection, although its mechanism has so far been unknown. In this study, we show that wild-type MV can infect and produce syncytia in human polarized epithelial cell lines independently of SLAM and CD46 (a receptor for the vaccine strains of MV). Progeny viral particles are released exclusively from the apical surface of these polarized epithelial cell lines. We have also identified amino acid residues on the MV attachment protein that are likely to interact with a putative receptor on epithelial cells. All of these residues have aromatic side chains and may form a receptor-binding pocket located in a different position from the putative SLAM-and CD46-binding sites on the MV attachment protein. Thus, our results indicate that MV has an intrinsic ability to infect both polarized epithelial and immune cells by using distinctive receptorbinding sites on the attachment protein corresponding to each of their respective receptors. The ability of MV to infect polarized epithelial cells and its exclusive release from the apical surface may facilitate its efficient transmission via aerosol droplets, resulting in its highly contagious nature.Measles remains a major cause of childhood morbidity and mortality worldwide despite the availability of efficacious vaccines. Measles virus (MV), an enveloped RNA virus belonging to the genus Morbillivirus in the family Paramyxoviridae, is transmitted via aerosol droplets and considered to be one of the most contagious human pathogens. MV has two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins, which are responsible for receptor binding and membrane fusion, respectively (18). MV enters a cell by membrane fusion at the cell surface. The attachment of the H protein to a cellular receptor is believed to induce the conformational change of the H protein, as well as that of the F protein, which promotes the fusion of the viral envelope with the host cell membrane. MV also causes cell-cell fusion in susceptible cells. The signaling lymphocyte activation molecule (SLAM), also known as CD150, has been identified as a receptor for MV (10,21,47). SLAM is expressed on immune cells, such as activated lymphocytes, mature dendritic cells, and macrophages, providing a good explanation for the lymphotropism and immunosuppressive nature of MV (4, 51). Although CD46, a ubiquitously expressed complement regulatory molecule, functions as a receptor for the vaccine strains of MV (8, 30), a great majority of viruses circulating in measles patients use SLAM, but not CD46, as a receptor (35,51). A recent study of MV infection in macaq...

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Rapid Detection of Measles Virus III Skin Rashes by Immunofluorescence

Cited by 42 publications

References 10 publications

Wild-Type Measles Virus is Intrinsically Dual-Tropic

Wild-Type Measles Virus is Intrinsically Dual-Tropic

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

Measles Virus Infects both Polarized Epithelial and Immune Cells by Using Distinctive Receptor-Binding Sites on Its Hemagglutinin

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