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Viruses Mar 2020Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding... (Review)
Review
Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding RNAs (ncRNAs). Herein, we review the current knowledge regarding ncRNAs, both host- and virus-derived, and their role in respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections. RSV is known as the most common cause of lower respiratory tract infection (LRTI) in children, while hMPV is also a significant contributor to LRTI in the pediatrics population. Although RSV and hMPV are close members, belonging to the family, they induce distinct changes in the ncRNA profile. Several types of host ncRNAs, including long ncRNA (lncRNA), microRNAs (miRNAs), and transfer RNA (tRNA)-derived RNA fragments (tRFs), are involved as playing roles in RSV and/or hMPV infection. Given the importance of ncRNAs in regulating the expression and functions of genes and proteins, comprehensively understanding the roles of ncRNAs in RSV/hMPV infection could shed light upon the disease mechanisms of RSV and hMPV, potentially providing insights into the development of prevention strategies and antiviral therapy. The presence of viral-derived RNAs and the potential of using ncRNAs as diagnostic biomarkers are also discussed in this review.
Topics: Animals; Biomarkers; Disease Resistance; Drug Discovery; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Metapneumovirus; MicroRNAs; Paramyxoviridae Infections; RNA, Untranslated; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32245206
DOI: 10.3390/v12030345 -
Human Vaccines & Immunotherapeutics Dec 2023Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in...
Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine's efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.
Topics: Child; Humans; Aged; Metapneumovirus; mRNA Vaccines; Epitopes, B-Lymphocyte; T-Lymphocytes, Cytotoxic; Respiratory Tract Infections; Epitopes, T-Lymphocyte; Computational Biology; Vaccines, Subunit
PubMed: 38172569
DOI: 10.1080/21645515.2023.2293300 -
Frontiers in Immunology 2024Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several...
INTRODUCTION
Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied.
METHODS
Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group.
RESULTS
We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8 T cells and memory precursor effector CD8 T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level.
DISCUSSION
To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
Topics: Child; Mice; Humans; Animals; Child, Preschool; Aged; Metapneumovirus; CD8-Positive T-Lymphocytes; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Paramyxoviridae Infections; Adaptive Immunity; Respiratory Tract Infections; Inflammation; Immunoglobulin A
PubMed: 38404579
DOI: 10.3389/fimmu.2024.1330209 -
Viruses Mar 2021Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to... (Review)
Review
Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to health burden. The worldwide economic and social impact of this virus is significant and must be addressed. The structural components of hMPV (either proteins or genetic material) can be detected by several receptors expressed by host cells through the engagement of pattern recognition receptors. The recognition of the structural components of hMPV can promote the signaling of the immune response to clear the infection, leading to the activation of several pathways, such as those related to the interferon response. Even so, several intrinsic factors are capable of modulating the immune response or directly inhibiting the replication of hMPV. This article will discuss the current knowledge regarding the innate and adaptive immune response during hMPV infections. Accordingly, the host intrinsic components capable of modulating the immune response and the elements capable of restricting viral replication during hMPV infections will be examined.
Topics: Adaptive Immunity; Child, Preschool; Host Microbial Interactions; Humans; Immunity, Innate; Metapneumovirus; Paramyxoviridae Infections
PubMed: 33809875
DOI: 10.3390/v13030519 -
Immunology and Allergy Clinics of North... Aug 2019Respiratory viruses other than rhinovirus or respiratory syncytial virus, including human metapneumovirus, influenza virus, and human bocavirus, are important pathogens... (Review)
Review
Respiratory viruses other than rhinovirus or respiratory syncytial virus, including human metapneumovirus, influenza virus, and human bocavirus, are important pathogens in acute wheezing illness and asthma exacerbations in young children. Whether infection with these viruses in early life is associated with recurrent wheezing and/or asthma is not fully investigated, although there are data to suggest children with human metapneumovirus lower respiratory tract infection may have a higher likelihood of subsequent and recurrent wheezing several years after initial infection.
Topics: Asthma; Bocavirus; Host-Pathogen Interactions; Humans; Metapneumovirus; Odds Ratio; Orthomyxoviridae; Respiratory Sounds; Respiratory Syncytial Viruses; Rhinovirus; Virus Diseases
PubMed: 31284928
DOI: 10.1016/j.iac.2019.03.007 -
Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations.Clinical Infectious Diseases : An... Jan 2021Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated...
BACKGROUND
Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens.
METHODS
Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression.
RESULTS
HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43-9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59-.99) and atypical (OR, 0.39; 95% CI, .19-.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55-1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87-7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32-2.50) were more severe than HMPV (reference), but all other pathogens had similar severity.
CONCLUSIONS
Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.
Topics: Adult; Child; Hospitalization; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 32010955
DOI: 10.1093/cid/ciaa088 -
The burden of RSV, hMPV, and PIV amongst hospitalized adults in the United States from 2016 to 2019.Journal of Hospital Medicine Jul 2024Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract...
BACKGROUND
Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States.
METHODS
We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus.
RESULTS
We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV.
CONCLUSIONS
RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.
Topics: Humans; United States; Respiratory Syncytial Virus Infections; Male; Female; Cross-Sectional Studies; Retrospective Studies; Metapneumovirus; Paramyxoviridae Infections; Middle Aged; Hospitalization; Adult; Aged; Respiratory Syncytial Virus, Human; Length of Stay
PubMed: 38462763
DOI: 10.1002/jhm.13320 -
Seminars in Respiratory and Critical... Aug 2020Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. There is growing appreciation of the burden of noninfluenza viral pathogens in... (Review)
Review
Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. There is growing appreciation of the burden of noninfluenza viral pathogens in CAP. Due to multiple factors including pneumococcal vaccination programs, declining rates of cigarette smoking, an aging population, and increasingly sensitive diagnostic tests, respiratory viruses are now the most common pathogens detected in CAP, outpacing . Noninfluenza respiratory pathogens are widely accepted as causal pathogens in CAP including in immunocompetent patients. This review provides an overview of five noninfluenza respiratory viral pathogens commonly implicated in CAP pathogenesis: rhinovirus, human metapneumovirus, respiratory syncytial virus, human parainfluenza virus, and human adenoviruses. Nucleic acid amplification testing platforms and their impact on antimicrobial stewardship efforts are also considered.
Topics: Adenoviruses, Human; Coinfection; Community-Acquired Infections; Humans; Immunocompromised Host; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 3, Human; Pneumonia, Viral; Respiratory Syncytial Virus, Human; Rhinovirus; Virus Diseases
PubMed: 32629492
DOI: 10.1055/s-0040-1710537 -
Transplantation Dec 2021Human metapneumovirus (HMPVi) and parainfluenza virus (PIVi) infections are common community-acquired infections in lung transplant recipients (LTRs), but data are...
BACKGROUND
Human metapneumovirus (HMPVi) and parainfluenza virus (PIVi) infections are common community-acquired infections in lung transplant recipients (LTRs), but data are extremely limited.
METHODS
A retrospective study including all LTRs at the Johns Hopkins Hospital during July 2010-June 2019 with positive HMPV and PIV polymerase chain reaction respiratory specimens was performed.
RESULTS
Thirty-one HMPV- and 53 PIV-infected LTRs were identified. LTRs with HMPVi and PIVi had similar baseline characteristics, infection parameters, treatment allocation, and allograft function outcomes. Among entire cohort, 31.6% had chronic allograft dysfunction (CLAD) stage progression within 1 y postinfections (29.2% versus 35.5% for PIVi versus HMPVi, respectively, P = 0.56). In forced expiratory volume in 1 s percent (FEV1%) trajectory analysis showed steadily decline of FEV1 across time among CLAD stage progressors from both viruses. FEV1% decline ≥10% at 90 d had adjusted hazard ratio for CLAD stage progression of 18.4 (4.98-67.76) and 4.6 (1.36-15.34) for PIVi and HMPVi, respectively. PIVi caused higher donor-specific antigen development (11.8% versus 3.2%, P = 0.18) and 1-y mortality (9.4% versus 0%, P = 0.11), compared with HMPVi, even though the results were not statistically significant. Ribavirin did not show protective effect, and mycophenolate discontinuation during infection did not increase risk of CLAD stage progression.
CONCLUSIONS
One-third of HMPV- and PIV-infected LTRs developed CLAD stage progression within 1 y. The lack of early lung function recovery may predict long-term CLAD progression.
Topics: Allografts; Humans; Lung; Lung Transplantation; Metapneumovirus; Paramyxoviridae Infections; Retrospective Studies; Transplant Recipients
PubMed: 33496558
DOI: 10.1097/TP.0000000000003645 -
Pathogens (Basel, Switzerland) Feb 2020Human metapneumovirus (HMPV) is an important human pathogen that, along with respiratory syncytial virus (RSV), is a major cause of respiratory tract infections in young... (Review)
Review
Human metapneumovirus (HMPV) is an important human pathogen that, along with respiratory syncytial virus (RSV), is a major cause of respiratory tract infections in young infants. Development of an effective vaccine against Pneumoviruses has proven to be particularly difficult; despite over 50 years of research in this field, no vaccine against HMPV or RSV is currently available. Recombinant chimeric viruses expressing antigens of other viruses can be generated by reverse genetics and used for simultaneous immunization against more than one pathogen. This approach can result in the development of promising vaccine candidates against HMPV, and several studies have indeed validated viral vectors expressing HMPV antigens. In this review, we summarize current efforts in generating recombinant chimeric vaccines against HMPV, and we discuss their potential optimization based on the correspondence with RSV studies.
PubMed: 32093057
DOI: 10.3390/pathogens9020135