Notes from the Field: Severe Human Metapneumovirus Infections — North Dakota, 2016

Midgley, Claire M; Baber, Jill; Biggs, Holly M.; Singh, Twila; Feist, Michelle; Miller, Tracy K.; Kruger, Kirby; Gerber, Susan I.; Watson, John T.; Howell, Molly

doi:10.15585/mmwr.mm6618a7

Cited by 6 publications

(3 citation statements)

References 5 publications

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“…HMPV is thought to have a zoonotic origin following a spill over event from an avian reservoir host species 2 . The pathogen is now known to cause both upper and lower respiratory tract infections, including both bronchiolitis and pneumonia, with children being the most affected demographic [3][4][5][6] . It is estimated that 5% to 12% of hospitalizations due to viral respiratory infections of children are caused by HMPV 3,7 .…”

Section: Main Textmentioning

confidence: 99%

Structure of the N-RNA/P interface reveals mode of L/P attachment to the nucleocapsid of human metapneumovirus

Whitehead¹,

Decool²,

Leyrat³

et al. 2023

Preprint

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Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The polymerase complex of HMPV consists of two obligate components, the L polymerase and its cofactor, the phosphoprotein P. During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within multimerized N nucleoproteins. An essential interaction between N and a C-terminal region of P is required for tethering of the L/P polymerase to the RNA template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how L/P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to polymerase activity assays and imaging of inclusion bodies in transfected cells. We report a 2.9 A resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.

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Section: Main Textmentioning

confidence: 99%

Structure of the N-RNA/P interface reveals mode of L/P attachment to the nucleocapsid of human metapneumovirus

Whitehead¹,

Decool²,

Leyrat³

et al. 2023

Preprint

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“…LRT disease can be severe, particularly when an individual is exposed to virus for the first time. Outcomes can include bronchiolitis and pneumonia and can result in death [37].…”

Section: The Disease and Risk Factorsmentioning

confidence: 99%

Human Metapneumovirus: A Largely Unrecognized Threat to Human Health

et al. 2020

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Human metapneumovirus (HMPV) infects most children by five years of age. The virus can cause both upper and lower respiratory tract disease and can be life threatening. High-risk populations include young children who are exposed to virus for the first time and the elderly. Currently, there is no standard treatment nor licensed vaccine for HMPV, although several attractive vaccine candidates have been developed for pre-clinical studies. A raised awareness of the impact of HMPV on public health is needed to drive research, complete vaccine development, and thereby prevent significant virus-associated morbidities and mortalities worldwide.

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“…[1][2][3] The viruses primarily cause respiratory symptoms that are usually mild to moderate in healthy adolescents and adults, but can lead to severe illness in young children, the elderly, and individuals with compromised immune systems. [4][5][6][7][8][9][10] Since people are unlikely to seek medical attention for a mild to moderate illness and laboratory testing can be limited in clinical settings, it is difficult to assess the magnitude of outbreaks and overall disease burden. There are currently no approved treatments beyond supportive care, making prevention a crucial part of protecting at risk populations.…”

Section: Introductionmentioning

confidence: 99%

Household transmission of human metapneumovirus and seasonal coronavirus

Bell,

He,

Norton

et al. 2024

Epidemiol. Infect.

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We analyzed data from a community-based acute respiratory illness study involving K-12 students and their families in southcentral Wisconsin and assessed household transmission of two common seasonal respiratory viruses-human metapneumovirus (HMPV) and human coronaviruses OC43 and HKU1 (HCOV). We found secondary infection rates of 12.2% (95% CI: 8.1%-17.4%) and 19.2% (95% CI: 13.8%-25.7%) for HMPV and HCOV, respectively. We performed individual-and family-level regression models and found that HMPV transmission was positively associated age of index case (individual model: p=.016; family model: p=.004) and HCOV transmission was positively associated with household density (family model: p=.048). We also found that the age of the non-index case was negatively associated with transmission of both HMPV (Individual model: p=.049) and HCOV (Individual model: p=.041), but we attributed this to selection bias from original study design. Understanding household transmission of common respiratory viruses like HMPV and HCOV may help to broaden our understanding of the overall disease burden and establish methods to prevent the spread of disease from low-to high-risk populations. KEY POINTS Infection of school-aged children is an important driver of respiratory virus transmission within households. As the age of an index case increases, the likelihood of human metapneumovirus transmission increases within households. As household density increases, the likelihood of seasonal coronavirus transmission increases within households.

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Notes from the Field: Severe Human Metapneumovirus Infections — North Dakota, 2016

Cited by 6 publications

References 5 publications

Structure of the N-RNA/P interface reveals mode of L/P attachment to the nucleocapsid of human metapneumovirus

Structure of the N-RNA/P interface reveals mode of L/P attachment to the nucleocapsid of human metapneumovirus

Human Metapneumovirus: A Largely Unrecognized Threat to Human Health

Household transmission of human metapneumovirus and seasonal coronavirus

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