-
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 -
Viruses Jun 2013Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their... (Review)
Review
Lung dendritic cells (DC) play a fundamental role in sensing invading pathogens, as well as in the control of tolerogenic responses in the respiratory tract. Their strategic localization at the site of pathogen entry makes them particularly susceptible to initial viral invasion. Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) belong to the Paramyxoviridae family, within the Pneumovirus and Metapneumovirus genera, respectively. hRSV and hMPV are significant human respiratory pathogens that cause similar clinical manifestations and affect many of the same subpopulations. However, they differentially activate the host immune response, including DC, which represents a fundamental link between the innate and adaptive immune response. In this review, the role of DC in the immune response against hRSV and hMPV infections, as well as the inhibitory effects of these paramyxoviruses on the DC immunity will be discussed.
Topics: Dendritic Cells; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 23787776
DOI: 10.3390/v5061553 -
Indian Journal of Pediatrics Sep 2023
Topics: Infant; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 37247182
DOI: 10.1007/s12098-023-04653-2 -
Journal of Virology Sep 2022The production of type I interferon (IFN) is the hallmark of the innate immune response. Most, if not all, mammalian viruses have a way to circumvent this response....
The production of type I interferon (IFN) is the hallmark of the innate immune response. Most, if not all, mammalian viruses have a way to circumvent this response. Fundamental knowledge on viral evasion of innate immune responses may facilitate the design of novel antiviral therapies. To investigate how human metapneumovirus (HMPV) interacts with the innate immune response, recombinant viruses lacking G, short hydrophobic (SH), or M2-2 protein expression were assessed for IFN induction in A549 cells. HMPV lacking G or SH protein expression induced similarly low levels of IFN, compared to the wild-type virus, whereas HMPV lacking M2-2 expression induced significantly more IFN than the wild-type virus. However, sequence analysis of the genomes of M2-2 mutant viruses revealed large numbers of mutations throughout the genome. Over 70% of these nucleotide substitutions were A-to-G and T-to-C mutations, consistent with the properties of the adenosine deaminase acting on RNA (ADAR) protein family. Knockdown of ADAR1 by CRISPR interference confirmed the role of ADAR1 in the editing of M2-2 deletion mutant virus genomes. More importantly, Northern blot analyses revealed the presence of defective interfering RNAs (DIs) in M2-2 mutant viruses and not in the wild-type virus or G and SH deletion mutant viruses. DIs are known to be potent inducers of the IFN response. The presence of DIs in M2-2 mutant virus stocks and hypermutated virus genomes interfere with studies on HMPV and the innate immune response and should be addressed in future studies. Understanding the interaction between viruses and the innate immune response is one of the barriers to the design of antiviral therapies. Here, we investigated the role of the G, SH, and M2-2 proteins of HMPV as type I IFN antagonists. In contrast to other studies, no IFN-antagonistic functions could be observed for the G and SH proteins. HMPV with a deletion of the M2-2 protein did induce type I IFN production upon infection of airway epithelial cells. However, during generation of virus stocks, these viruses rapidly accumulated DIs, which are strong activators of the type I IFN response. Additionally, the genomes of these viruses were hypermutated, which was prevented by generating stocks in ADAR knockdown cells, confirming a role for ADAR in hypermutation of HMPV genomes or DIs. These data indicate that a role of the HMPV M2-2 protein as a bona fide IFN antagonist remains elusive.
Topics: A549 Cells; Adenosine Deaminase; Antiviral Agents; Humans; Immunity, Innate; Interferon Type I; Metapneumovirus; RNA-Binding Proteins; Viral Proteins
PubMed: 35975999
DOI: 10.1128/jvi.00723-22 -
Viruses Dec 2012Human metapneumovirus (hMPV) is a recently identified RNA virus belonging to the Paramyxoviridae family, which includes several major human and animal pathogens.... (Review)
Review
Human metapneumovirus (hMPV) is a recently identified RNA virus belonging to the Paramyxoviridae family, which includes several major human and animal pathogens. Epidemiological studies indicate that hMPV is a significant human respiratory pathogen with worldwide distribution. It is associated with respiratory illnesses in children, adults, and immunocompromised patients, ranging from upper respiratory tract infections to severe bronchiolitis and pneumonia. Interferon (IFN) represents a major line of defense against virus infection, and in response, viruses have evolved countermeasures to inhibit IFN production as well as IFN signaling. Although the strategies of IFN evasion are similar, the specific mechanisms by which paramyxoviruses inhibit IFN responses are quite diverse. In this review, we will present an overview of the strategies that hMPV uses to subvert cellular signaling in airway epithelial cells, the major target of infection, as well as in primary immune cells.
Topics: Humans; Immune Evasion; Immunity, Innate; Interferons; Metapneumovirus; Viral Proteins; Virulence Factors
PubMed: 23223197
DOI: 10.3390/v4123551 -
Influenza and Other Respiratory Viruses Nov 2022Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the...
BACKGROUND
Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children.
METHODS
NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via real-time reverse-transcription polymerase chain reaction (RT-PCR). We used classical additive decomposition analysis to assess the temporal trends, and generalized growth models (GGMs) were used to estimate effective reproduction numbers.
RESULTS
From 2011 to 2016, there were 564 hMPV symptomatic infections, yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3509 acute lower respiratory infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (rate ratio 5.5 95% CI 4.1, 7.4 p < 0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were detected reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011 to 2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4).
CONCLUSIONS
Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.
Topics: Child; Cohort Studies; Humans; Infant; Influenza, Human; Metapneumovirus; Nicaragua; Paramyxoviridae Infections; Prospective Studies; Respiratory Tract Infections
PubMed: 35965382
DOI: 10.1111/irv.13034 -
Virulence Aug 2017Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting... (Review)
Review
Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections. In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses.
Topics: Adaptive Immunity; Aged; Animals; B-Lymphocytes; Child; Cytokines; Humans; Immune Evasion; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; T-Lymphocytes; Virus Replication
PubMed: 27911218
DOI: 10.1080/21505594.2016.1265725 -
Emerging Infectious Diseases Feb 2006We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of...
We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.
Topics: Adolescent; Adult; Cell Line; Child; Child, Preschool; Female; Glycoproteins; Humans; Male; Metapneumovirus; Molecular Sequence Data; Paramyxoviridae Infections; Peru; Pharynx; Phylogeny; Population Surveillance; Sequence Analysis, DNA; Specimen Handling; Viral Proteins
PubMed: 16494771
DOI: 10.3201/eid1202.051133 -
Virology Journal Mar 2024Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV... (Review)
Review
Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.
Topics: Infant; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections; Antiviral Agents; China; Vaccines
PubMed: 38454484
DOI: 10.1186/s12985-024-02327-9 -
Frontiers in Immunology 2023Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility to bacterial...
Human metapneumovirus (HMPV) is a pneumovirus that may cause severe respiratory disease in humans. HMPV infection has been found to increase susceptibility to bacterial superinfections leading to increased morbidity and mortality. The molecular mechanisms underlying HMPV-mediated increase in bacterial susceptibility are poorly understood and largely understudied. Type I interferons (IFNs), while critical for antiviral defenses, may often have detrimental effects by skewing the host immune response and cytokine output of immune cells. It is currently unknown if HMPV skews the inflammatory response in human macrophages triggered by bacterial stimuli. Here we report that HMPV pre-infection impacts production of specific cytokines. HMPV strongly suppresses IL-1β transcription in response to LPS or heat-killed and , while enhancing mRNA levels of IL-6, TNF-α and IFN-β. We demonstrate that in human macrophages the HMPV-mediated suppression of IL-1β transcription requires TANK-binding kinase 1 (TBK1) and signaling via the IFN-β-IFNAR axis. Interestingly, our results show that HMPV pre-infection did not impair the LPS-stimulated activation of NF-κB and HIF-1α, transcription factors that stimulate IL-1β mRNA synthesis in human cells. Furthermore, we determined that sequential HMPV-LPS treatment resulted in accumulation of the repressive epigenetic mark H3K27me3 at the promoter. Thus, for the first time we present data revealing the molecular mechanisms by which HMPV shapes the cytokine output of human macrophages exposed to bacterial pathogens/LPS, which appears to be dependent on epigenetic reprogramming at the promoter leading to reduced synthesis of IL-1β. These results may improve current understanding of the role of type I IFNs in respiratory disease mediated not only by HMPV, but also by other respiratory viruses that are associated with superinfections.
Topics: Humans; Cytokines; Metapneumovirus; Superinfection; Transcription, Genetic; Interleukin-1beta; Interferon-beta; Bacterial Infections; Paramyxoviridae Infections
PubMed: 37435074
DOI: 10.3389/fimmu.2023.1173605