Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Laksono, Brigitta M.; Vries, Rory D. de; Verburgh, R. Joyce; Visser, Eline G.; Jong, Alwin de; Fraaij, Pieter L. A.; Ruijs, Wilhemina L.M.; Nieuwenhuijse, David F.; Ham, Henk-Jan van den; Koopmans, Marion; Zelm, Menno C. van; Osterhaus, Albert D. M. E.; Swart, Rik L. de

doi:10.1038/s41467-018-07515-0

Cited by 98 publications

(97 citation statements)

References 44 publications

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“…During a recent measles outbreak in the Netherlands, families in communities with low vaccination rates consented to provide blood samples. Plasma was collected before and after laboratory-confirmed MV infection from 77 unimmunized children with a mean age of 9 (SD ± 2) years, plus five unimmunized children who remained uninfected during the study (24). Of the 77 children, 34 were reported to have mild measles and 43 to have severe measles [detailed in (24)].…”

Section: Measuring the Consequences Of Measles On Immune Memorymentioning

confidence: 99%

“…Plasma was collected before and after laboratory-confirmed MV infection from 77 unimmunized children with a mean age of 9 (SD ± 2) years, plus five unimmunized children who remained uninfected during the study (24). Of the 77 children, 34 were reported to have mild measles and 43 to have severe measles [detailed in (24)]. The mean time between sample collections was 10 weeks, and mean time of collection after MV infection was 7 weeks (table S1).…”

Section: Measuring the Consequences Of Measles On Immune Memorymentioning

confidence: 99%

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Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Mina

Kula

Leng

et al. 2019

Science

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361

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Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.

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Section: Measuring the Consequences Of Measles On Immune Memorymentioning

confidence: 99%

Section: Measuring the Consequences Of Measles On Immune Memorymentioning

confidence: 99%

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Mina

Kula

Leng

et al. 2019

Science

Self Cite

361

289

View full text Add to dashboard Cite

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“…Following entry of MV into the respiratory tract, the primary infection of myeloid cells leads to a cell-associated viremia mediated by CD150 + lymphocytes, resulting in systemic disease [7–9]. During a clinically silent incubation phase of 7 to 10 days, circulating MV-infected lymphocytes migrate into various tissues and transmit the virus to susceptible tissue-resident CD150 + immune cells and nectin-4 + epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…Basolateral infection of respiratory epithelial cells leads to the apical release of nascent virions into the lumen of the respiratory tract [10–12]. Shedding is associated with the onset of prodromal clinical signs such as fever and cough [9, 13]. Maculopapular skin rash and conjunctivitis follow a few days later [9] and are associated with onset of MV-specific cellular immune responses [13].…”

Section: Introductionmentioning

confidence: 99%

“…Shedding is associated with the onset of prodromal clinical signs such as fever and cough [9, 13]. Maculopapular skin rash and conjunctivitis follow a few days later [9] and are associated with onset of MV-specific cellular immune responses [13]. Patients with a compromised cellular immune system do not develop rash or conjunctivitis, but are at high risk of developing severe disease [14].…”

Section: Introductionmentioning

confidence: 99%

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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 and Rubella Viruses

Crooke,

Coughlin,

Perelygina

2023

ClinMicroNow

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Measles virus is the prototypic member of the genus Morbillivirus in the family Paramyxoviridae , and it is the only member of the genus that causes human disease. Characteristic cytopathic effects of measles virus infection include giant multinucleated cells (Warthin‐Finkeldey giant cells) as well as intracytoplasmic and intranuclear cellular inclusions. Rubella virus was historically classified in the family Togaviridae as the sole member of the genus Rubivirus ; however, in 2018, rubella virus (and the genus Rubivirus ) was reclassified as the sole member the new family Matonaviridae . The present description of laboratory testing for rubella emphasizes identification of postnatal and congenital rubella cases. However, in the United States, much of the testing is for assessing immunity to rubella, since health care providers should test all pregnant women for immunity by a serum IgG test at the earliest prenatal visit.

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Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Cited by 98 publications

References 44 publications

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

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

Measles and Rubella Viruses

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