Measles Virus Host Invasion and Pathogenesis

Laksono, Brigitta M.; Vries, Rory D. de; McQuaid, Stephen; Duprex, W. Paul; Swart, Rik L. de

doi:10.3390/v8080210

Cited by 154 publications

(130 citation statements)

References 84 publications

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“…identification of two receptors CD150/SLAMF1 and Nectin-4 [18,19], as well as a better understanding of pathogenesis (reviewed here: [20]). However, PPRV-specific knowledge still lags behind that of MeV and RPV.…”

Section: Pprv Virology and Epidemiology: Improving Our Fundamental Unmentioning

confidence: 99%

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

Baron

Diop

Njeumi

et al. 2017

Journal of General Virology

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Peste des petits ruminants virus (PPRV) is a significant pathogen of small ruminants and is prevalent in much of Africa, the Near and Middle East and Asia. Despite the availability of an efficacious and cheap live-attenuated vaccine, the virus has continued to spread, with its range stretching from Morocco in the west to China and Mongolia in the east. Some of the world's poorest communities rely on small ruminant farming for subsistence and the continued endemicity of PPRV is a constant threat to their livelihoods. Moreover, PPRV's effects on the world's population are felt broadly across many economic, agricultural and social situations. This far-reaching impact has prompted the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) to develop a global strategy for the eradication of this virus and its disease. PPRV is a morbillivirus and, given the experience of these organizations in eradicating the related rinderpest virus, the eradication of PPRV should be feasible. However, there are many critical areas where basic and applied virological research concerning PPRV is lacking. The purpose of this review is to highlight areas where new research could be performed in order to guide and facilitate the eradication programme. These areas include studies on disease transmission and epidemiology, the existence of wildlife reservoirs and the development of next-generation vaccines and diagnostics. With the support of the international virology community, the successful eradication of PPRV can be achieved.

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Section: Pprv Virology and Epidemiology: Improving Our Fundamental Unmentioning

confidence: 99%

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

Baron

Diop

Njeumi

et al. 2017

Journal of General Virology

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“…Inter-host variations have been implicated in the differences in the outcomes realized with the same virus (13). In the extreme, a single outcome may be realized, such as with measles virus infection, which is nearly always cleared (50), or HIV infection, which invariably leads to persistence (51). While we have addressed the roles of key factors such as NK cells and innate immune responses, further embellishments of our motif are necessary to describe the influence of other factors.…”

Section: Discussionmentioning

confidence: 99%

A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections

Baral¹,

Antia

Dixit

2019

Preprint

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Some viral infections culminate in very different outcomes in different individuals. They can be rapidly cleared in some, cause persistent infection in others, and mortality from immunopathology in yet others. The conventional view is that the different outcomes arise as a consequence of the complex interactions between a large number of different factors (virus, different immune cells and cytokines). Here, we identify a simple dynamical motif comprising the essential interactions between antigens and CD8 T cells and posit it as predominantly determining the outcomes. Antigen can activate CD8 T cells, which in turn can kill infected cells. Sustained antigen stimulation, however, can cause CD8 T cell exhaustion, compromising effector function. Using mathematical modelling, we show that the motif comprising these interactions recapitulates all the outcomes observed. The motif presents a new conceptual framework to understand the variable outcomes of infection. It also explains a number of confounding experimental observations, including the variation in outcomes with the viral inoculum size, the evolutionary advantage of exhaustion in preventing lethal pathology, the ability of NK cells to act as rheostats tuning outcomes, and the role of the innate immune response in the spontaneous clearance of hepatitis C. Interventions that modulate the interactions in the motif may present novel routes to clear persistent infections or limit immunopathology.

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“…MV infects the respiratory epithelial cells and is shed apically into the mucus lining the lumen of the upper and lower respiratory tract, which is void of CD150 or nectin-4. The virus is thus transported to the throat by the mucociliary escalator and expelled into the air by coughing [52]. The role of MV skin infection in viral transmission is still a subject of speculation.…”

Section: Discussionmentioning

confidence: 99%

Measles skin rash: infection of lymphoid and myeloid cells in the dermis precedes viral dissemination to keratinocytes in the epidermis

Laksono

Fortugno

Nijmeijer

et al. 2019

Preprint

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2 precedes viral dissemination to keratinocytes in the epidermis 3 4 The pathogenesis of measles skin rash 5 6 2 24 Abstract 25 Measles is characterised by fever and a maculopapular skin rash, which is associated with 26 immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin 27 biopsies from humans and non-human primates (NHPs) with measles rash have identified 28 MV-infected keratinocytes and mononuclear cells in the epidermis, around hair follicles and 29 near sebaceous glands. Here, we address the pathogenesis of measles skin rash by combining 30 data from experimentally infected NHPs, ex vivo infection of human skin sheets and in vitro 31 infection of primary human keratinocytes. Longitudinal analysis of the skin of experimentally32 MV-infected NHPs demonstrated that infection in the skin precedes onset of rash by several 33 days. MV infection was initiated in lymphoid and myeloid cells in the dermis before 34 dissemination to the epidermal keratinocytes. These data were in good concordance with ex 35 vivo MV infections of human skin sheets, in which dermal cells were more targeted than the 36 epidermal ones. To address viral dissemination to the epidermis and to determine whether 37 the dissemination is receptor-dependent, we performed experimental infections of primary 38 keratinocytes collected from healthy or nectin-4-deficient donors. These experiments 39 demonstrated that MV infection of keratinocytes is nectin-4-dependent, and nectin-4 40 expression was higher in differentiated than in proliferating keratinocytes. Based on these 41 data, we hypothesise that measles skin rash is initiated by migrating MV-infected 42 lymphocytes that infect dermal skin-resident CD150 + immune cells. The infection is 43 subsequently disseminated from the dermal papillae to nectin-4 + keratinocytes in the basal 44 epidermis. Lateral spread of MV infection is observed in the superficial epidermis, most likely 45 due to the higher level of nectin-4 expression on differentiated keratinocytes. Finally, MV-46 infected cells are cleared by infiltrating immune cells, causing hyperaemia and oedema, which 47 give the appearance of morbilliform skin rash.3 48 49 Author Summary 50 Several viral infections are associated with skin rash, including parvovirus B19, human 51 herpesvirus type 6, dengue virus and rubella virus. However, the archetype virus infection 52 that leads to skin rash is measles. Although all of these viral exanthemata often appear similar, 53 their pathogenesis is different. In the case of measles, the appearance of skin rash is a sign 54 that the immune system is clearing MV-infected cells from the skin. How the virus reaches 55 the skin and is locally disseminated remains unknown. Here we combine observations and 56 expertise from pathologists, dermatologists, virologists and immunologists to delineate the 57 pathogenesis of measles skin rash. We show that MV infection of dermal myeloid and 58 lymphoid cells precedes viral dissemination to the epidermal keratinocytes. We specula...

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Measles Virus Host Invasion and Pathogenesis

Cited by 154 publications

References 84 publications

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections

Measles skin rash: infection of lymphoid and myeloid cells in the dermis precedes viral dissemination to keratinocytes in the epidermis

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