Human metapneumovirus ( HMPV or hMPV ) is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR (RNA arbitrarily primed PCR ) technique for identification of unknown viruses growing in cultured cells. As of 2016, it was the second most common cause (after respiratory syncytial virus (RSV)) of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic .
41-468: The peak age of hospitalization for infants with HMPV occurs between 6–12 months of age, slightly older than the peak of RSV, which is around 2–3 months. The clinical features and severity of HMPV are similar to those of RSV. HMPV is also an important cause of disease in older adults. Human metapneumovirus was first discovered in 2001 in the Netherlands by Bernadette G. van den Hoogen and her colleagues. hMPV
82-494: A cell infected by more than one virus strain. This occurs either by Homologous recombination of the nucleic acid strands or by reassortment of genomic segments. Both these and mutation within the virus have been suggested as ways in which influenza and other viruses evolve. An example of a recombinant virus is Western equine encephalitis virus (WEE), which is a recombinant virus between two other closely related yet distinct encephalitis viruses. In addition, reassortment
123-568: A lower risk of side effects. Despite the superior filtration capability of N95 filtering facepiece respirators measured in vitro, insufficient clinical evidence has been published to determine whether standard surgical masks and N95 filtering facepiece respirators are equivalent to preventing respiratory infections in healthcare workers. Adults in intensive care units (ICU) have a higher risk of acquiring an RTI. A combination of topical and systematic antibiotics taken prophylactically can prevent infection and improve adults' overall mortality in
164-477: A metapneumovirus and its use of humans as a host organism. HMPV was responsible for 12% of cases of acute respiratory tract illness in otherwise-healthy children in a US outpatient clinic and 15% and 8% of cases (respectively) of community-acquired pneumonia requiring hospitalization in children under and over the age of 5 in the United States. The virus is distributed worldwide and, in temperate regions, has
205-633: A seasonal distribution generally following that of RSV and influenza virus during late winter and spring. Serologic studies have shown that by the age of five, virtually all children worldwide have been exposed to the virus. Despite near universal infection during early life, reinfections are common in older children and adults. Human metapneumovirus may cause mild upper respiratory tract infection (the common cold ). However, premature infants, immunocompromised persons, and older adults >65 years are at risk for severe disease and hospitalization. In some studies of hospitalizations and emergency room visits, HMPV
246-567: A set of advanced Pulmonary Function Testing will be based on abnormally high values in previous test results. A 2014 systematic review of clinical trials does not support routine rapid viral testing to decrease antibiotic use for children in emergency departments. It is unclear if rapid viral testing in the emergency department for children with acute febrile respiratory infections reduces the rates of antibiotic use, blood testing , or urine testing . The relative risk reduction of chest x-ray utilization in children screened with rapid viral testing
287-426: Is 77% compared with controls. In 2013 researchers developed a breath tester that can promptly diagnose lung infections. Bacteria are unicellular organisms present on Earth can thrive in various environments, including the human body. Antibiotics are a medicine designed to treat bacterial infections that need a more severe treatment course; antibiotic use is not recommended for common bacterial infections as
328-557: Is between 40 and 60%. Therefore, relative humidity in this range can help lessen the risk of aerosol transmission. Respiratory infections often have strong seasonal patterns, with temperate climates more affected during the winter . Several factors explain winter peaks in respiratory infections, including environmental conditions and changes in human behaviors. Viruses that cause respiratory infections are affected by environmental conditions like relative humidity and temperature. Temperate climate winters have lower relative humidity, which
369-432: Is dominant over the others and none of them are known to cause varying levels of severity. hMPV is most likely spread from infected individuals to others through 1. secretions from coughing and sneezing, 2. close personal contact (ex. touching, shaking hands, etc), and 3. touching objects with viruses on them then touching your mouth, nose, or eyes. Development of a reliable antiviral therapy treatment or vaccine to prevent
410-734: Is high; 47 million prescriptions in the United States in 2018 were made for infections that do not need antibiotics to be treated with. It is recommended to avoid antibiotic use unless bacterial infections are severe, transmissible, or have a high risk of further complications if left untreated. Unnecessary use of antibiotics could increase antibiotic-resistant infections, affect the digestive system , create allergic reactions , and other intense side effects. A study published in JAMA found that narrow-spectrum antibiotics, such as amoxicillin, are just as effective as broad-spectrum alternatives for treating acute respiratory tract infections in children, but have
451-483: Is known to increase the transmission of influenza . Of the viruses that cause respiratory infections in humans, most have seasonal variation in prevalence. Influenza, Human orthopneumovirus (RSV), and human coronaviruses are more prevalent in the winter. Human bocavirus and Human metapneumovirus occur year-round, rhinoviruses (which cause the common cold ) occur mostly in the spring and fall, and human parainfluenza viruses have variable peaks depending on
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#1733093946897492-438: Is nearly as common and as severe as influenza in older adults. HMPV is associated with more severe disease in people with asthma and adults with chronic obstructive pulmonary disease ( COPD ). Numerous outbreaks of HMPV have been reported in long-term care facilities for children and adults, causing fatalities. The genomic organisation of HMPV is similar to RSV ; however, HMPV lacks the non-structural genes , NS1 and NS2, and
533-534: Is still a relatively new virus and has not yet been researched very heavily, hMPV and its replication cycle still have a lot of mystery surrounding them. However, researchers have been able to elucidate some principal steps of hMPV's replication cycle, basing their approach and experimentation on the current knowledge we have of the viral life cycles and reproductive measures of the rest of the Paramyxoviridae family. With that being said, it has been determined that
574-549: Is that hMPV's fusion events occur at acidic pH levels while other viruses’ fusion events occur at neutral pH levels; however, more research needs to be conducted in this area to get a better understanding of what is different about the hMPV fusion mechanism and why. Although its specific function is uncertain, it is important to note the presence of the SH glycoprotein which seemingly does not have any effects on replication kinetics, cytopathic effects, or plaque formation of hMPV. After fusion,
615-419: Is yet known, but ribavirin has shown effectiveness in an animal model. American pharmaceutical corporation Moderna has conducted a clinical trial for a candidate modRNA vaccine against metapneumovirus. As of October 2019, the vaccine candidate has passed through phase I , with reports that the vaccine is well-tolerated at all dose levels at two months, and provokes an immune response which boosts
656-558: The glottis or vocal cords; sometimes, it is taken as the tract above the cricoid cartilage . This part of the tract includes the nose , sinuses , pharynx , and larynx . Typical infections of the upper respiratory tract include tonsillitis , pharyngitis , laryngitis , sinusitis , otitis media , certain influenza types, and the common cold . Symptoms of URIs can include cough , sore throat , runny nose , nasal congestion , headache , low-grade fever , facial pressure, and sneezing . The lower respiratory tract consists of
697-432: The immune system will resolve such infections. This medicine does not effectively treat a viral infection like sore throats , influenza , bronchitis , sinusitis and common respiratory tract infections. This is because antibiotics were developed to target features of bacteria that are not present in viruses, and so antibiotics are ineffective as antiviral agents . The CDC has reported that antibiotic prescription
738-412: The trachea (windpipe), bronchial tubes , bronchioles , and the lungs . Lower respiratory tract infections (LRIs) are generally more severe than upper respiratory infections. LRIs are the leading cause of death among all infectious diseases . The two most common LRIs are bronchitis and pneumonia . Influenza affects both the upper and lower respiratory tracts, but more dangerous strains such as
779-449: The F and G genes showed that subtype B was associated with increased cough duration and increased general respiratory systems compared to HMPV-A. hMPV is estimated to have a 3–6 day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection. But because it
820-436: The G protein is not required for rest of the replication cycle. Next in the cycle is the fusion of the viral and host membranes which is likely mediated by the F protein. Though the fusion mechanism is very similar to that of other Paramyxoviridae family members and involves conformational changes of the F protein, the mechanism for hMPV does not depend on the G protein for fusion like its family members, showing consistency with
861-490: The HMPV antisense RNA genome contains eight open reading frames in slightly different gene order than RSV (viz. 3’-N-P-M-F-M2-SH-G-L-5’). HMPV is genetically similar to the avian metapneumoviruses A, B and in particular type C. Phylogenetic analysis of HMPV has demonstrated the existence of two main genetic lineages termed subtype A and B containing within them the subgroups A1/A2 and B1/B2 respectively. Genotyping based on sequences of
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#1733093946897902-518: The ICU for adult patients receiving mechanical ventilation for at least 48 hours, and topical antibiotic prophylaxis probably reduces respiratory infections but not mortality. However, the combination of treatments cannot rule out the relevant contribution in the systemic component of the observed reduction of mortality. There is no sufficient evidence to recommend that antibiotics be used to prevent complications from an RTI of unknown cause in children under
943-565: The action of viral fusion proteins on the surface, effectively spreading the virus's genome. The rest of the replication cycle following RNA and viral protein synthesis are unclear and require further research. HMPV infects airway epithelial cells in the nose and lung. HMPV is thought to attach to the target cell via the glycoprotein (G) protein interactions with heparan sulfate and other glycosaminoglycans. The HMPV fusion (F) protein encodes an RGD (Arg-Gly-Asp) motif that engages RGD-binding integrins as cellular receptors, then mediates fusion of
984-599: The age of 5 years old. High-quality clinical research in the form of randomized controlled trials assessed the effectiveness of Vitamin D, another review of poorer quality RCTs addressed the effectiveness of immunostimulants for preventing respiratory tract infections. Despite some uncertainty due to small study sizes, there is some evidence that exercise may reduce severity of symptoms but had no impact on number of episodes or number of symptom days per episode. Viruses that cause RTI are more transmissible at very high or low relative humidity ; ideal humidity for indoor spaces
1025-560: The cell membrane and viral envelope in a pH-independent fashion, likely within endosomes . HMPV then induces the response of chemokines and cytokines such as IL-6, IFN-alpha, TNF-alpha, IL-2, and macrophage inflammatory proteins, which in turn leads to peribronchiolar and perivascular infiltration and inflammation. The identification of HMPV has predominantly relied on reverse-transcriptase polymerase chain reaction ( RT-PCR ) technology to amplify directly from RNA extracted from respiratory specimens. Alternative more cost-effective approaches to
1066-466: The detection of HMPV by nucleic acid -based approaches have been employed and these include: Though hMPV was first discovered and identified in 2001, serological studies showed that hMPV, or a close relative of it, had already been circulating for at least 50 years. From this information, it is clear that the virus had not just “jumped” from birds, or some other animal reservoir, to humans shortly before its discovery. So far, peak infection from hMPV in
1107-434: The development of hMPV in the natural host. There are no conclusive studies to date; however, it is likely that transmission occurs by contact with contaminated secretions, via droplet, aerosol, or fomite vectors. Hospital-acquired infections with human metapneumovirus have been reported. HMPV has been shown to circulate during fall and winter months with alternating predominance of a single subtype each year. No treatment
1148-446: The first step of the hMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. This G protein contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor to facilitate its binding; however, because recombinant viruses that lack the G protein have still been able to replicate in vitro and in vivo , it seems that attachment via
1189-422: The hMPV F gene allows for neutralizing antibodies against both parainfluenza and hMPV. However promising these results and trials may seem, it is important to note that these experiments have limitations including their small-population animal models. Overall, while vaccines and antiviral therapy treatments are in the works, the biggest difficulty that researchers face at the moment is the limited data available about
1230-439: The highly pernicious H5N1 tend to bind to receptors deep in the lungs. Pulmonary Function Testing (PFT) allows for the evaluation and assessment of airways, lung function, as well as specific benchmarks to diagnose an array of respiratory tract infections. Methods such as gas dilution techniques and plethysmography help determine the functional residual capacity and total lung capacity. To discover whether or not to perform
1271-411: The lower or upper respiratory tract . An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI or LRTI). Lower respiratory infections, such as pneumonia , tend to be far more severe than upper respiratory infections, such as the common cold . The upper respiratory tract is considered the airway above
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1312-459: The northern hemisphere is in late winter and early spring, but it can be found globally across all continents and its distribution is very complex and dynamic. Researchers have found that hMPV is mostly localized and can differ significantly from community to community, allowing for the possibility of the strain in one location one year to be most similar to the strain in a different location the next year. This phenomenon has actually been recorded with
1353-521: The novel virus. It was not until researchers began applying molecular biology techniques that the genetic characteristics and portions of the genomic sequences of the virus could be identified; these techniques included the randomly primed PCR technique which obtained the limited sequence data needed to reveal a clear relationship between this new virus and the avian pneumovirus. It was this close relationship to AMPV that gave rise to this new virus being named human metapneumovirus to reflect both its identity as
1394-445: The previously mentioned idea that the G protein is not necessary for subsequent steps of the hMPV replication cycle. Moreover, the fusion function of the F protein has been proven by its ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif , which is speculated to be the trigger for membrane fusion events. One main difference between hMPV and other Paramyxoviridae viruses’ fusion mechanisms though
1435-535: The production of neutralising antibodies . Human metapneumovirus was first reported in 2001 and avian metapneumovirus in the 1970s. There are at least four lineages of human metapneumovirus—A1, A2, B1 and B2. Avian metapneumovirus has been divided into four subgroups—A, B, C and D. Bayesian estimates suggest that human metapneumovirus emerged 119–133 years ago and diverged from avian metapneumovirus around 1800. Respiratory tract infection Respiratory tract infections ( RTIs ) are infectious diseases involving
1476-416: The specific strain. Enteroviruses , with the exception of rhinoviruses, tend to peak in the summer. Recombinant virus A recombinant virus may occur naturally or be produced by recombining pieces of DNA or RNA in a laboratory . This may be used to produce viral vaccines or gene therapy vectors. The term is also used to refer to naturally occurring recombination between virus genomes in
1517-412: The spread of hMPV has yet to occur, but there does seem to be promising developments in that area. In some vaccine trials, researchers have observed how a live recombinant human parainfluenza virus that contains the hMPV F gene can induce hMPV-specific antibodies and can protect experimental animals from hMPV. Another similar study demonstrated how a chimeric bovine /human parainfluenza virus 3 expressing
1558-527: The vRNA and bind to each other to form the polymerase complex so that the genomic RNA can act as a matrix for viral transcription and replication in the cytoplasm. The final step in the replication process of hMPV that is relatively certain is the journeying of the envelope glycoproteins (F, G, and SH) to zones of membranous accumulation via the Golgi apparatus to be exposed at the surface of infected cells. This allows infected cells to merge with adjacent cells through
1599-497: The viral ribonucleoprotein (RNP) containing negative-sense viral RNA (vRNA) genome is released into the cytoplasm and acts as a template for mRNA and antigenomic cRNA synthesis. From here, most of our knowledge about hMPV transcription is derived from what we already know about RSV and other Paramyxoviridae viruses, including that leader and trailer sequences in the genome are partially complementary and act as promoters for transcription. We see that proteins N, P, and L dissociate from
1640-601: The virus strains in Australia in 2001; in France in 2000 and 2002; in Canada in 1999, 2000, 2001, and 2002; in Israel in 2002; and in the Netherlands in 2001 all being very closely related based on their F gene sequences. There are at least two major genotypes of hMPV (A and B) that circulate during community outbreaks and each genotype has two of its own, but as of now, it seems that no one strain
1681-426: Was first detected in the respiratory secretions of 28 young children in the Netherlands and had initially stood out from other common respiratory viruses because the testing methods van den Hoogen et al. had tried using (immunological assays using virus-specific antibodies and PCR-based methods using virus genome-specific primers) were only able to test for known respiratory viruses and, therefore, were unable to identify