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Human metapneumovirus (HMPV) is a virus that causes acute respiratory infection, mostly in children, the elderly, and people with weak immunity. Its symptoms resemble a common cold but can cause respiratory infections like pneumonia and bronchiolitis. It was first identified by Bernadette G. van den Hoogen et al. from 28 children in the Netherlands in 2001. HMPV belongs to the family Pneumoviridae and genus Metapneumovirus.
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Habitat of Human metapneumovirus (HMPV)
- Human metapneumovirus (HMPV) primarily infects humans, with animal reservoirs unknown.
- HMPV is a virus that infects the upper and lower respiratory tract, including the nose, throat, and lungs.
- They usually affect young children, older adults, and immunocompromised people.
- HMPV is a seasonal disease that normally occurs in the winter and early spring, similar to RSV and flu.
- HMPV can survive on surfaces for several hours, which may cause indirect transmission.
Structure of Human metapneumovirus (HMPV)
- Human metapneumovirus (HMPV) is an enveloped, negative-sense single-stranded RNA (-ssRNA) virus with a pleomorphic shape.
- They are 150 to 600 nanometers in diameter.
- The structure of HMPV includes an outer envelope (lipid bilayer) with three membrane surface glycoproteins: fusion protein (F), glycoprotein (G), and small hydrophobic protein (SH). They are in the form of spikes of approximately 13-17 nm.
- The fusion protein (F) and glycoprotein (G) play an important role in the virus to invade the host cell membrane and initiate the infection (replication cycle).
- The matrix protein (M) is located on the inner side of the outer envelope (lipid bilayer). This M protein acts as a bridge between the envelope and nucleocapsid.
Genome of Human metapneumovirus (HMPV)
- The genome of HMPV comprises negative-sense single-stranded RNA (-ssRNA) and contains eight genes that code for nine proteins.
- Its genome is 13.2 Kb.
- The order of the genes in the genome (from 3′ to 5′ end) is N–P–M–F–M2–SH–G–L.
- The proteins are:
- Nucleoprotein (N protein): helps in the formation of nucleocapsid.
- Phosphoprotein (P protein): helps in viral replication and transcription.
- Matrix protein (M protein): helps in virus assembly and budding.
- Fusion glycoprotein (F protein): helps in the fusion of the virus into the host cell.
- Putative transcription factor (M2-1 protein): helps in transcriptional regulation.
- RNA synthesis regulatory factor (the M2-2 protein): helps in transcriptional regulation.
- Small hydrophobic glycoprotein (SH protein): Functions not clear; might help in virus-host interaction.
- Attachment glycoprotein (G protein): helps in the attachment of the virus into the host cell.
- Viral polymerase (L protein): helps in viral replication and transcription.
- Whole genome analysis of HMPV showed that the virus exists in two genotypes, A and B (Barbara Huck et al. 2006).
- Based upon the sequence variability of the attachment (G) and fusion (F) surface glycoproteins, these two genotypes are further divided into subgroups A1, A2, B1, and B2.
- Subgroup A2 is again subdivided into A2a and A2b.
- Recently, unique HMPV variants with 180 nt duplication (nt-dup) in the G gene and a 111 nt-dup in the G gene have been reported (Zhibo Xie et al. 2021).
Replication of Human metapneumovirus (HMPV)
The replication of Human metapneumovirus (HMPV) takes place in the cytoplasm of host cells, primarily in the epithelial cell of the respiratory tract.
- Attachment: The virus is attached to the host cell with the help of glycoprotein (G). The glycoprotein (G) contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor, which helps to bind the virus.
- Fusion and Entry: A fusion of HMPV and the host plasma membrane takes place with the help of fusion protein (F). The fusion protein (F) has the ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif. HMPV fusion occurs at acidic pH levels. Then, the viral ribonucleoprotein (RNP), which contains negative-sense viral RNA (vRNA genome), is released into the host cytoplasm.
- Transcription and Translation: The nucleoprotein (N protein), phosphoprotein (P protein), and viral polymerase (L protein) separate from the vRNA and bind to each other to form the polymerase complex. The viral RNA-dependent RNA polymerase transcribes the negative-sense viral RNA (vRNA) into messenger RNA (mRNA). These mRNAs are then translated by the host’s ribosomal machinery to produce viral proteins necessary for replication and assembly.
- Replication: When sufficient viral proteins are made, replication of the viral genome occurs.
- Assembly: Newly synthesized viral genomes from replication are encapsidated by nucleoproteins, which form ribonucleoprotein complexes. The ribonucleocapsid interacts with the matrix protein (M) under the host’s plasma membrane, where viral glycoproteins (F, G, and SH) are transported and embedded.
- Budding and Release: The assembled virions bud from the host cell membrane via the ESCRT complex, releasing the virion.
Epidemiology of HMPV Infection
- HMPV infects all ages people worldwide, with higher severity in young children, older adults, and immunocompromised people.
- Most children are infected with HMPV by the age of 5.
- HMPV infection mostly occurs in winter and early spring.
- An increase in the incidence of HMPV is reported with increasing distance from the equator (Medscape).
- A study done at the Vanderbilt Vaccine Clinic in Nashville, a primary care clinic, has shown that HMPV was responsible for 12% of cases of acute respiratory tract illness in healthy children in a U.S. outpatient clinic (John V Williams et al. 2007).
- When there is an infection in childhood, there is a high chance of re-infections throughout life.
Symptoms of HMPV Infection
Symptoms typically develop 3 to 6 days (incubation period) after exposure to the virus and usually last for 2 to 5 days. Symptoms are similar to a cold.
Common Symptoms of HMPV Infection
- Cough
- Fever
- Runny Nose
- Nasal Congestion
- Sore Throat
- Fatigue
- Rash
Severe Symptoms of HMPV Infection
- Wheezing
- Difficulty Breathing
- Bronchiolitis
- Bronchitis
- Pneumonia
- Asthma or COPD flare-ups
- Ear infections
- Croup
Transmission of Human metapneumovirus (HMPV)
HMPV is transmitted from one person to another through:
- personal and close contact with droplets/aerosols from an infected person.
- coughing, sneezing, splitting.
- direct contact by shaking hands, hugging, kissing, or touching an infected person.
- touching objects or surfaces like door handles, tissues, utensils, phones, toys, etc., containing viruses and touching the mouth, nose, or eyes.
Risk Factors of HMPV Infection
HMPV poses higher risks to certain groups as follows:
- Young Children below 5 years old.
- Older Adults over 65 years old.
- People with weak immune systems, like individuals with HIV/AIDS, cancer treatments, organ transplants, or chronic illnesses.
- People with chronic respiratory conditions like Asthma and Chronic obstructive pulmonary disease (COPD).
- Premature infants may have underdeveloped lungs and immune systems, making them more vulnerable to HMPV infections.
Pathogenesis of HMPV Infection
HMPV infects the respiratory tract, causing infections, inflammation, and damage to the airway epithelium.
Host Immune Response
- HMPV interferes with the host’s innate immune system using specific mechanisms.
- The virus antagonizes cellular responses by regulating pattern recognition receptors, such as toll-like receptors, retinoic acid-inducible gene-like receptors, and other signaling molecules.
- HMPV infections may lead to a minimal and late immune response and delayed cytotoxic T-lymphocyte activity with impaired virus clearance during primary infection.
- Infection interferes with dendritic cell activity and reduces antigen-specific T-cell activation.
- Thus, virus clearance remains incomplete, and there is an increased chance of re-infection.
- The proliferation of antigen-specific CD4+ T cells is restricted, and the production of long-term immunity is impaired.
- HMPV infection induces toll-like receptor-dependent cellular signaling.
- HMPV infection inhibits the production of type I and type III interferons responsible for antiviral defense.
Mucin 19
- The mucus production is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown.
- Mucins are a major component of mucus and could impact how the host responds to infections.
- Mucin 19 is predominantly expressed in the respiratory tract when infected with HMPV.
- Mucin 19 activates the immune response to HMPV and HMPV-induced pathogenesis.
Inflammation
- HMPV infection triggers the release of chemokines and cytokines, leading to immune cell infiltration and inflammation.
- HMPV infection induces pulmonary inflammatory changes in BALB/c mice and cotton rats and leads to an increase in the levels of interleukins (IL-2, IL-8, IL-4), interferon (IFN-α), macrophage inflammatory protein 1α, and monocyte chemotactic proteins in the bronchoalveolar lavage fluid and the lungs.
- These changes further lead to perivascular and peribronchiolar infiltration and inflammation.
Tissue Damage
- Viral cytopathic effects lead to damage to the respiratory epithelium.
- The formation of intra-alveolar foamy and haemosiderin-laden macrophages, smudge cells, alveolar damage, and hyaline membrane disease are seen in HMPV infection.
Recovery
- The immune system of the body eventually controls and clears the infection.
- In some cases, the infection can be more severe in persons with risk factors. In this case, recovery may be prolonged.
Clinical Manifestation of HMPV Infection
Human metapneumovirus (HMPV) causes both upper respiratory tract infections and lower respiratory tract diseases. The clinical manifestation of HMPV depends on various factors like age, health conditions, and immune status of individuals.
Upper Respiratory Tract Infections
- Persistent cough along with mucus production
- Runny or stuffy nose
- Throat pain
- Mild to moderate fever, Headache
- Sense of tiredness or malaise
Lower Respiratory Tract Infections
- Wheezing: high pitch whistling sound while breathing
- Shortness of breath or difficulty in breathing
- Chest Retraction
- Exacerbations of asthma and COPD: HMPV increases the severity of asthma and COPD
Severe Clinical Manifestations
- Bronchiolitis: It is a common lung infection caused by viruses in children and infants. There is an inflammation of small airways (bronchioles) in the lungs that causes difficulty in breathing. It causes swelling and mucus formation in the bronchioles.
- Bronchitis: It is an inflammation of airways in the lungs (lining of the bronchial tubes). It may be acute or chronic.
- Pneumonia: It is an inflammation of the lungs that affects small air sacs called alveoli. Air sacs are filled with mucus or pus.
Secondary Infections
- Central nervous system diseases: Some studies have shown that HMPV infection may cause diseases of the central nervous system (CNS) like seizures and encephalitis (John C Arnold et al. 2009).
- Otitis Media: One study shows that 50% of children with HMPV infection were diagnosed with otitis media (John V Williams et al. 2007).
Diagnosis of Human metapneumovirus (HMPV)
Diagnosis is typically done through a physical examination, patient history, and lab tests. Laboratory tests are done to confirm the presence of Human metapneumovirus (HMPV) in the body.
1. Clinical Evaluations
- Risk Factor Assessments: Taking health history.
- Symptoms Assessments: Some of the symptoms, such as cough, fever, nasal congestion, and shortness of breath, are checked for preliminary purposes.
2. Laboratory Test
A. Sample
Samples are collected from the upper respiratory tract (usually nose or throat) using aspirates. In case of severe conditions, bronchoalveolar lavage or bronchoscopy may be performed.
B. Virus Culture
Various cell lines, such as Vero cells, HEp-2 cells, Hep G2 cells, 293 cells, and LLC-MK2 cells, are used to grow and isolate HMPV.
C. Antigen Detection
HMPV antigen is detected using the anti-hMPV antibody in direct immunofluorescence or ELISA-based assays. It is less sensitive than molecular methods like PCR.
D. Molecular Diagnosis
PCR techniques like reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and multiplex RT-PCR (mRT-PCR) can be used to diagnose HMPV accurately. mRT-PCR has an advantage over immunofluorescence tests because it can detect undetectable co-infections, even with low viral loads.
E. Chest Radiography
Chest X-rays may help to find hyperinflation, peribronchial thickening, or infiltrates, suggesting bronchiolitis or pneumonia.
Treatment of HMPV Infection
- Currently, there is no specific antiviral therapy to treat HMPV.
- Treatment focuses on relieving symptoms and providing supportive care.
- Infective people can take over-the-counter medications, such as pain relievers, decongestants, and cough suppressants.
- Medications such as acetaminophen or ibuprofen can be used to reduce fever and alleviate body aches.
- Oxygen therapy can be given if we have a hard time breathing.
- We can use a room humidifier or take a hot shower to help ease a sore throat and cough and drink plenty of liquids to stay hydrated.
- IV fluids can be given to stay hydrated.
- Steroids can reduce inflammation and might ease some of the symptoms.
- Most people recover from HMPV infection within 7 to 10 days.
- However, there have been some studies about the possibilities of using ribavirin, immunoglobulin, fusion inhibitors, and small interfering ribonucleic acids to treat and control HMPV infection (Swagatika Panda et al. 2014).
Do we need antibiotics for HMPV Infection?
No, we don’t need to use antibiotics to treat HMPV Infection. Since antibiotics only work for bacteria, they do not work for human metapneumovirus. But, if the person gets bacterial pneumonia simultaneously (secondary infection), antibiotics can be used to treat any secondary infection like bacterial pneumonia with the recommendation of doctors and physicians.
Vaccines for HMPV Infection
- Currently, as of January 2025, there are no specific vaccines to prevent HMPV.
- Several vaccine candidates against HMPV have been tested in rodent and non-human primate models (Marie-Ève Hamelin et al. 2007).
- Some of the vaccines and clinical trials which are under development are as follows:
Prevention and Control of HMPV Infection
- Proper and frequent hand washing.
- Avoid touching eyes, nose, or mouth with unwashed hands.
- Avoid close contact with people who are sick.
- Cover the mouth and nose when coughing and sneezing.
- Wear a nose and mouth mask.
- Avoid sharing cups and utensils with others.
- Cleaning and disinfecting surfaces.
- Stay at home when sick.
- Healthcare facilities should follow infection prevention and control guidelines to manage patients with suspected or confirmed HMPV.
- Public health authorities should monitor HMPV activity and provide timely information to the public.
Human Metapneumovirus (HMPV) vs. SARS-CoV-2
Feature | Human Metapneumovirus (HMPV) | SARS-CoV-2 |
---|---|---|
Virus Family | Paramyxoviridae | Coronaviridae |
Size | 150–600 nanometers (nm) | 60-140 nanometres (nm) |
Genomic Structure | Single-stranded, negative-sense RNA (-ssRNA) | Single-stranded, positive-sense RNA (+ssRNA) |
Transmission | Primarily through respiratory droplets; contact with contaminated surfaces. | Primarily through respiratory droplets and contact with contaminated surfaces. |
Incubation Period | Approximately 3-6 days. | Approximately 2-14 days. |
Symptoms | Mild: Runny nose, sore throat, cough, fever.
Moderate: Persistent cough, wheezing, fatigue. Severe: Bronchitis, bronchiolitis, pneumonia, especially in infants, older adults, and immunocompromised individuals. |
Primarily through respiratory droplets, aerosols, and contact with contaminated surfaces. |
Severity | Generally mild to moderate; severe cases can occur in high-risk groups. | Ranges from asymptomatic to severe; higher risk of severe disease and mortality compared to HMPV. |
Seasonality | Initial outbreaks occur in winter; subsequent waves occur year-round. | Initial outbreaks in winter; subsequent waves have occurred year-round. |
Diagnosis | No vaccine is currently available; research is ongoing. | – RT-PCR testing. – Antigen tests. – Serology for antibodies. |
Treatment | Supportive care; no specific antiviral treatment available. | – Mild cases: Supportive care. – Severe cases: Hospitalization, oxygen therapy, antiviral treatments (e.g., remdesivir), corticosteroids. |
Vaccines | Multiple vaccines have been developed and administered globally (e.g., mRNA vaccines and viral vector vaccines). | Multiple vaccines developed and administered globally (e.g., mRNA vaccines, viral vector vaccines). |
Preventive Measures | – Hand hygiene. – Respiratory etiquette. – Avoiding close contact with infected individuals. – Surface disinfection. |
– Hand hygiene. – Mask-wearing. – Physical distancing. – Vaccination. – Surface disinfection. |
Global Impact | It causes seasonal outbreaks and is generally less disruptive on a global scale. | Mild to Moderate: Fever, dry cough, fatigue, loss of taste or smell.
Severe: Difficulty breathing, chest pain, confusion; can lead to acute respiratory distress syndrome (ARDS) and multi-organ failure, especially in older adults and those with underlying health conditions. |
References
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