Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Messling, Véronika von; Milošević, Dragana; Cattaneo, Roberto

doi:10.1073/pnas.0403597101

Cited by 179 publications

(215 citation statements)

References 43 publications

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“…High levels of epithelial cell infection are observed in peripheral tissues in other morbillivirus infections, for example acute distemper in ferrets (von Messling et al, 2004). This may be due to differences in the dynamics of virulent canine distemper virus (CDV) infection in the ferret in comparison with MV in the macaque model.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Although the major sites of Morbillivirus propagation are lymphoid cells and organs (44), CDV, MV and rinderpest virus can invade the central nervous systems of their hosts. Lymphoid and neuronal cell death is most likely due to apoptosis, rather than necrosis.…”

Section: Discussionmentioning

confidence: 99%

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

Suter¹,

Chein²,

Messling

et al. 2005

Clinical Cancer Research

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Purpose: Measles virus (MV) causes the regression of human lymphoma xenografts. The purpose of this study was to determine if canine lymphoid cells could be infected in vitro with MV or canine distemper virus (CDV, the canine Morbillivirus equivalent of MV) and determine if in vitro viral infection leads to apoptotic cell death. Experimental Design: Reverse transcriptase-PCR was used to examine the expression of both signal lymphocyte activation molecule (CD150) and membrane cofactor molecule (CD46) mRNA. An attenuated CDV expressing enhanced green fluorescent protein was used to infect canine cells in vitro. Both flow cytometry and reverse transcriptase-PCR was used to document CDV infection. Cell death was examined using a propidium iodide staining assay and Annexin V binding. Results: Canine lymphoid cell lines and neoplastic B and T lymphocytes collected from dogs with spontaneous lymphoma expressed the Morbillivirus receptor CD150 mRNA. In contrast, only neoplastic lymphocytes expressed detectable levels of CD46 mRNA. Although MV did not infect canine cells, CDV efficiently infected between 40% and 70% of all three canine lymphoid lines tested. More importantly, CDV infected 50% to 90% of neoplastic lymphocytes isolated from dogs with both B and T cell lymphoma. Apoptosis of CDV-infected cell lines was documented. Conclusions: Attenuated CDV may be a useful treatment for canine lymphoma. As such, dogs with lymphoma may represent a biologically relevant large animal model to investigate the feasibility, safety, and efficacy of Morbillivirus therapy in a clinical setting with findings that may have direct applicability in the treatment of human non-Hodgkin's lymphoma.

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“…CDV H and NiV G cytoplasmic domain truncation mutants were produced by PCR amplification using primers in which blocks of 10 residues in the N-terminal region immediately downstream of the start codon were progressively deleted. The CDV M (5804P strain) gene was amplified from the genomic plasmid p5804PeGFPH (von Messling et al, 2004), while the NiV M (Malaysia strain) gene was amplified from purified viral RNA. The 39 primers for the NiV M gene contained the coding sequence for the c-myc epitope tag (EQKLISEEDL) immediately upstream of the stop codon (Salditt et al, 2010), while the corresponding primer for CDV M contained no tag.…”

Section: Methodsmentioning

confidence: 99%

Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly

Sawatsky

Bente

Czub

et al. 2016

Journal of General Virology

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The amino-terminal cytoplasmic domains of paramyxovirus attachment glycoproteins include trafficking signals that influence protein processing and cell surface expression. To characterize the role of the cytoplasmic domain in protein expression, fusion support and particle assembly in more detail, we constructed chimeric Nipah virus (NiV) glycoprotein (G) and canine distemper virus (CDV) haemagglutinin (H) proteins carrying the respective heterologous cytoplasmic domain, as well as a series of mutants with progressive deletions in this domain. CDV H retained fusion function and was normally expressed on the cell surface with a heterologous cytoplasmic domain, while the expression and fusion support of NiV G was dramatically decreased when its cytoplasmic domain was replaced with that of CDV H. The cell surface expression and fusion support functions of CDV H were relatively insensitive to cytoplasmic domain deletions, while short deletions in the corresponding region of NiV G dramatically decreased both. In addition, the first 10 residues of the CDV H cytoplasmic domain strongly influence its incorporation into virus-like particles formed by the CDV matrix (M) protein, while the co-expression of NiV M with NiV G had no significant effect on incorporation of G into particles. The cytoplasmic domains of both the CDV H and NiV G proteins thus contribute differently to the virus life cycle.

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Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Cited by 179 publications

References 43 publications

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

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

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly

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