Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection

Lormeau, Barbara; Foulongne, Vincent; Baccino, É.; Adriansen, Aurélie; Pidoux, Odile; Prodhomme, O.; Haquet, A.; Guyon, G.; Jeziorski, Éric

doi:10.1016/j.arcped.2019.10.002

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…In addition, fatal hMPV has been observed in one child during an outbreak of hMPV in a daycare center. 17 hMPV is also a significant cause of febrile respiratory illness in HIV-infected patients 18 , and has been linked to exacerbations of chronic obstructive pulmonary disease 19 . Co-circulation of hMPV was observed during the SARS outbreak of 2003, suggesting interactions with other circulating respiratory viruses.…”

Section: Introductionmentioning

confidence: 99%

Antibody recognition of the Pneumovirus fusion protein trimer interface

Huang¹,

Diaz

Mousa

2020

Preprint

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13Human metapneumovirus is a leading cause of viral respiratory infection in children, and can 14 cause severe lower respiratory infection in infants, the elderly, and immunocompromised patients. 15However, there remain no licensed vaccines or specific treatments for hMPV infection. Although 16 the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological 17 properties of hMPV F are still poorly understood. To further define the humoral immune response 18 to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and 19 MPV465. Both mAbs are neutralizing in vitro and target a unique antigenic site harbored within 20 the trimeric interface of the hMPV F protein. We determined both MPV458 and MPV465 have 21 higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with 22 hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F 23 protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV 24 F protein, suggesting significant breathing of the hMPV F protein must occur for hMPV F protein 25 recognition of the novel epitope. In addition, significant glycan interactions were observed with a 26 somatically mutated light chain framework residue. The data presented identifies a novel epitope 27 on the hMPV F protein for structure-based vaccine design, and provides a new mechanism for 28 human antibody neutralization of viral glycoproteins.Human metapneumovirus (hMPV) is a leading cause of viral respiratory infections in children, the 32 majority of which are seropositive for hMPV by five years of age 1 . Although hMPV was discovered 33 in 2001 2 , there are no vaccines or therapeutics approved to prevent or treat viral infection. Similar 34 to other respiratory pathogens, children, the elderly, and the immunocompromised are the major 35 groups for which hMPV infection may require hospitalization [3][4][5][6][7][8][9][10][11] . Several reports have 36 demonstrated hMPV infection can be lethal in both adults and children. In particular, haemopoietic 37 stem cell transplant patients are at high risk of severe hMPV infection [10][11][12][13] , and several outbreaks 38 of hMPV in nursing homes have been reported [14][15][16] . In addition, fatal hMPV has been observed in 39 one child during an outbreak of hMPV in a daycare center. 17 hMPV is also a significant cause of 40 febrile respiratory illness in HIV-infected patients 18 , and has been linked to exacerbations of 41 chronic obstructive pulmonary disease 19 . Co-circulation of hMPV was observed during the SARS 42 outbreak of 2003, suggesting interactions with other circulating respiratory viruses. 20-22 43 44 hMPV circulates as two genotypes, A and B, and based on the sequence variability of the surface 45 proteins, hMPV is further grouped into four subgroups, A1, A2, B1, and B2 23,24 , and two additional 46 subgroups, A2a and A2b, have been proposed 12 . hMPV has three surface glycoproteins, the small 47 hydrophob...

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Section: Introductionmentioning

confidence: 99%

Antibody recognition of the Pneumovirus fusion protein trimer interface

Huang¹,

Diaz

Mousa

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In particular, haemopoietic stem cell transplant patients are at high risk of severe hMPV infection [ 10 – 13 ], and several outbreaks of hMPV in nursing homes have been reported [ 14 – 16 ]. In addition, fatal hMPV has been observed in one child during an outbreak of hMPV in a daycare center [ 17 ]. hMPV is also a significant cause of febrile respiratory illness in HIV-infected patients [ 18 ], and has been linked to exacerbations of chronic obstructive pulmonary disease [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Antibody recognition of the Pneumovirus fusion protein trimer interface

2020

View full text Add to dashboard Cite

Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory tract infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F remain poorly understood. To further define the humoral immune response to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and MPV465. Both mAbs are neutralizing in vitro and were determined to target a unique antigenic site using competitive biolayer interferometry. We determined both MPV458 and MPV465 have higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV F protein, suggesting significant breathing of the hMPV F protein must occur for host immune recognition of the novel epitope. In addition, significant glycan interactions were observed with a somatically mutated light chain framework residue. The data presented identifies a novel epitope on the hMPV F protein for epitope-based vaccine design, and illustrates a new mechanism for human antibody neutralization of viral glycoproteins.

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“…Patients going through an infection of HMPV usually have a favorable outcome; however, fatal cases have been reported in children without underlying medical conditions. Recently, two deaths due to HMPV infection were reported: the death of a 2.7 years old girl suffering from acute respiratory distress syndrome [16] and the death of a two-year-old old girl who suffered respiratory failure [17].…”

Section: Frequency Of Human Metapneumovirus In Pediatric Patientsmentioning

confidence: 99%

HMPV in Immunocompromised Patients: Frequency and Severity in Pediatric Oncology Patients

Martinez-Rodriguez

Baños-Lara

2020

Pathogens

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Cancer is the first cause of death by disease in childhood globally. The most frequent types of cancers in children and adolescents are leukemias, followed by brain and central nervous system tumors and lymphomas. The recovery rate of cancer in children is around 80% in developed countries and up to 30% in developing countries. Some of the main causes of complications in children and adolescents with cancer are respiratory viral infections, mainly in bone marrow-transplanted patients. Respiratory viruses have been detected in the bronchoalveolar lavage or nasal wash specimens from cancer patients with or without respiratory illness symptoms. Human metapneumovirus (HMPV) is within the ten most common viruses that are encountered in samples from pediatric patients with underlying oncology conditions. In most of cases, HMPV is found as the only viral agent, but co-infection with other viruses or with bacterial agents has also been reported. The discrepancies between the most prevalent viral agents may be due to the different populations studied or the range of viral agents tested. Some of the cases of infection with HMPV in cancer patients have been fatal, especially in those who have received a hematopoietic stem cell transplant. This review seeks to show a general view of the participation of HMPV in respiratory illness as a complication of cancer in childhood and adolescence. Keywords: pediatric cancer infections; HMPV; fatal cases in HSCT patients Childhood Cancer Global SituationCancer is the first cause of death by disease in children around the world. The five-year rate of survival of children who have cancer is up to 80% in developed countries, but for developing countries, the survival rate is less than 30% [1].According to a study based in cancer registries from 52 countries, the types of cancer in childhood (0-19 years old) during 2001-2010 were leukemia, lymphoma, central nervous system tumors, sympathetic nervous system tumors, retinoblastoma, renal tumors, hepatic tumors, bone tumors, soft tissue sarcomas, germ cell and gonadal tumors, epithelial tumors, and melanomas. The most frequent cancers in children of 0-14 years are leukemia, followed by lymphoma; meanwhile, for the ages of 15-19, the most prevalent is lymphoma, followed by leukemia [2].Cancer in childhood comprises only 1% of the total cancer cases worldwide; however, it has a dramatic impact. Recently the years of life lost due to cancer in childhood (0-19 years old) were calculated with global cancer registries in 2017, with a result of more than 11 million years [3].

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Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection

Cited by 4 publications

References 14 publications

Antibody recognition of the Pneumovirus fusion protein trimer interface

Antibody recognition of the Pneumovirus fusion protein trimer interface

Antibody recognition of the Pneumovirus fusion protein trimer interface

HMPV in Immunocompromised Patients: Frequency and Severity in Pediatric Oncology Patients

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