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According to the respiratory virus surveillance system of the Centers for Disease Control and Prevention (CDC), since the spring of this year, human metapneumovirus (HMPV) has been on the rise across various regions of the United States since the spring of this year. This virus has swept through the intensive care units and pediatric hospitals nationwide. The number of infections caused by this viral outbreak reached its peak in mid-March, with nearly 11% of tested samples showing HMPV positivity. This data represents an approximately 36% increase in positive cases compared to the seasonal peak of 7% before the outbreak. So, what exactly is this little-known virus? What are its symptoms and risks? How can it be prevented and treated?
1. What is human metapneumovirus?
2. Genome and structure of human metapneumovirus
3. Pathogenesis of human metapneumovirus
Human metapneumovirus (HMPV) is a single-stranded negative-strand RNA virus belonging to the family Paramyxoviridae. The virus is not novel and patients infected with HMPV have been identified as the causative agent of human respiratory infections in the Netherlands since 2001. Since then, Britain, Finland, Norway, Canada, Kenya, Australia, China (Beijing, Chongqing, Shenzhen and other regions) have also found cases of children infected with the virus.
The structure of the HMPV virus is depicted in Figure 1. The matrix protein (M) is located on the inner side of the virus's lipid bilayer. The viral particle contains three types of membrane surface glycoproteins: fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). Encapsidated within the viral envelope is the ribonucleoprotein (RNAP) complex consisting of the helical, genomic RNA wrapped by the nucleoprotein (N), the viral RNA-dependent, RNA polymerase (L), phosphoprotein (P), and matrix 2 protein (M2).
Figure 1. Schematic diagram of human metapneumovirus (HMPV) virus particle [1]
HMPV is transmitted through respiratory droplets in the air or by direct contact with infected individuals. The virus first infects respiratory epithelial cells. The fusion protein (F protein) and glycoprotein (G protein) on the virus surface bind to receptors on the host cell membrane, allowing the virus to enter the cell. Once inside the cell, the virus releases its genome, which is a negative-sense RNA. The RNA is transcribed into mRNA and translated into viral proteins. These proteins assist the virus in replicating its RNA genome, forming new virus particles. The newly formed virus particles then leave the infected cell, further infecting respiratory epithelial cells and spreading the virus.
To support research on the pathogenesis and prevention of HMPV, CUSABIO has responded promptly by organizing a series of research reagents related to HMPV studies.
| Code | Product Name | Target | Species |
|---|---|---|---|
| CSB-EP751042HDAM | Recombinant Human metapneumovirus Nucleoprotein(N) | N | Human metapneumovirus(strain CAN97-83)(HMPV) |
| CSB-EP761526HDAM | Recombinant Human metapneumovirus Matrix protein(M) | M | Human metapneumovirus(strain CAN97-83)(HMPV) |
| CSB-EP804307HDAM | Recombinant Human metapneumovirus Phosphoprotein(P) | P | Human metapneumovirus (strain CAN97-83) (HMPV) |
| CSB-BP761526HDAM | Recombinant Human metapneumovirus Matrix protein(M) | M | Human metapneumovirus(strain CAN97-83)(HMPV) |
| CSB-YP761526HDAM | Recombinant Human metapneumovirus Matrix protein(M) | M | Human metapneumovirus (strain CAN97-83) (HMPV) |
| CSB-CF751041HDAMa2 | Recombinant Human metapneumovirus Fusion glycoprotein F0(F) | F | Human metapneumovirus(strain CAN97-83)(HMPV) |
| CSB-EP751041HDAM1 | Recombinant Human metapneumovirus Fusion glycoprotein F0(F),partial | F | Human metapneumovirus (strain CAN97-83) (HMPV) |
HMPV generally leads to upper and lower respiratory tract infections with similar symptoms to other respiratory viral infections. The following are common symptoms of HMPV infection:
● Symptoms of upper respiratory tract infection: sore throat, stuffy nose, runny nose, sneezing, cough, expectoration, etc.
● Symptoms of lower respiratory tract infection: fever, dyspnea, chest stuffiness, and asthma; in severe cases, pneumonia and bronchitis develop.
Epidemiological characteristics of HMPV:
● Age group: Human beings of any age group can be infected with HMPV, and children and the elderly are the most vulnerable, especially infants under 5 years of age and the elderly over 65 years of age.
● Route of transmission: HMPV is mainly transmitted through air droplets. When an infected person coughs or sneezes or comes into close contact with others, the virus can be transmitted to others. In addition, surfaces or objects that come into contact with contamination may also become infected.
● Viral persistence: HMPV has a incubation period of 3-6 days and is highly infectious. The virus particles can survive for several hours to several days in the environment and are more easily transmitted in a closed collective environment.
● Seasonal epidemic: HMPV usually shows a high incidence in winter and spring.
● Immune status: People with a weak immune system or chronic respiratory disease are more susceptible to HMPV and may have a more serious condition.
Due to its high infectivity, HMPV poses a significant global burden of infection. Researchers estimate that approximately 10% to 12% of pediatric respiratory illnesses are associated with HMPV, with most cases presenting mild symptoms. However, about 5% to 16% of children may experience symptoms of lower respiratory tract infections such as pneumonia. A study published in The Lancet Global Health in 2020 revealed that in 2018, over 14 million children under the age of 5 were infected with HMPV, resulting in over 600,000 hospitalizations and more than 16,000 deaths.
● Clinical symptom assessment: The diagnosis is made by the physician based on the patient's history and symptoms associated with respiratory tract infection. HMPV infection has similar symptoms to other respiratory viral infections such as influenza virus, so clinical symptoms do not definitively diagnose HMPV infection and require laboratory tests to confirm.
● Laboratory tests: Molecular tests such as polymerase chain reaction (PCR) or real-time fluorescent quantitative PCR are performed on respiratory tract specimens (e.g., nasal swabs, pharyngeal swabs, sputum) to confirm infection by detecting and identifying RNA from HMPV.
● Symptomatic supportive treatment: Symptomatic treatment measures are taken in most patients with HMPV infection, including rest, maintenance of water intake, use of antipyretics (such as acetaminophen) for fever, and use of cough suppressants (upon doctor's recommendation) for cough relief.
● Oxygen therapy: Oxygen therapy may be needed to help relieve dyspnea and hypoxemia in severely ill patients.
● Immuno-boosting therapy: Immunocompromised patients may require additional therapeutic measures to boost immune function, such as the use of immunoglobulins (IVIG) or other immuno-boosting drugs.
● Antiviral drugs:
Currently, there are no specific antiviral drugs available for HMPV treatment. However, it is worth noting that the development of HMPV vaccines and antiviral drugs has gained attention. According to the Patsnap database, two HMPV vaccines, mRNA-1653 and mRNA-1365, developed by Moderna, are currently in Phase I clinical trials.
There have also been some new advances in the study of anti-HMPV drugs. Bergh [2] et al. identified 11 drug candidates with dose-dependent activity for the inhibition of HMPV infection, among which mycophenolic acid showed the highest inhibition because it blocked the synthesis of intracellular guanosine monophosphate. Furthermore, mycophenolic acid can achieve inhibitory levels at approved human oral doses, making it a potential candidate for drug repurposing.
Previously, human monoclonal antibodies MPE8 and 54G10 have been shown to reduce viral lung titers in HRSV-and HMPV-infected mouse models [3,4]. More recently, a study by Fausther-Bovendo [5] demonstrated that mAb 100 could reduce lung viral titers in mice infected with HRSV or HMPV, becoming the third human monoclonal antibody proven to block the replication of both viruses in vivo.
Currently, there is no specific antiviral therapy available for treating HMPV, nor is there a vaccine for preventing HMPV infection. However, there is no need to be overly anxious. By following these preventive measures, you can greatly reduce the risk of HMPV infection:
(1) Practice good hand hygiene by washing hands frequently.
(2) Practice proper coughing and sneezing etiquette, such as covering your mouth and nose with a tissue or your elbow.
(3) Maintain good indoor ventilation.
(4) Adopt a healthy lifestyle to enhance your immune system.
(5) Vaccination against influenza and pneumococcal infections may help reduce the severity of the disease and the risk of complications.
References
[1] J V Williams, R G Cox. Breaking In: Human Metapneumovirus Fusion and Entry[J]. Viruses, 2013, 5(1).
[2] A V D Bergh, P Guillon, M V Itzstein, et al. Drug Repurposing for Therapeutic Discovery against Human Metapneumovirus Infection[J]. Antimicrobial agents and chemotherapy, 66(10).
[3] D Corti, S Bianchi, F Vanzetta, et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 2013, 501, 439–443.
[4] J E Schuster, R G Cox, A K Hastings, et al. A Broadly Neutralizing Human Monoclonal Antibody Exhibits In Vivo Effificacy Against Both Human Metapneumovirus and Respiratory Syncytial Virus. J. Infect. Dis. 2014, 211, 216–225.
[5] H Fausther-Bovendo, H MarieEve, J Carbonneau, et al. A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice[J]. Biomedicines, 2022, 10(10).
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