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Open AccessArticle

Innate and Adaptive Immune Response to Pneumonia Virus of Mice in a Resistant and a Susceptible Mouse Strain

by Ellen R. T. Watkiss, Pratima Shrivastava, Natasa Arsic, Susantha Gomis and Sylvia Van Drunen Littel-van den Hurk

Viruses 2013, 5(1), 295-320; https://doi.org/10.3390/v5010295 - 21 Jan 2013

Cited by 20 | Viewed by 9472

Abstract

Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to [...] Read more.

Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessArticle

Diversity in Glycosaminoglycan Binding Amongst hMPV G Protein Lineages

by Penelope Adamson, Sutthiwan Thammawat, Gamaliel Muchondo, Tania Sadlon and David Gordon

Viruses 2012, 4(12), 3785-3803; https://doi.org/10.3390/v4123785 - 14 Dec 2012

Cited by 16 | Viewed by 7359

Abstract

We have previously shown that hMPV G protein (B2 lineage) interacts with cellular glycosaminoglycans (GAGs). In this study we examined subtypes A1, A2 and B1 for this interaction. GAG-dependent infectivity of available hMPV strains was demonstrated using GAG-deficient cells and heparin competition. We [...] Read more.

We have previously shown that hMPV G protein (B2 lineage) interacts with cellular glycosaminoglycans (GAGs). In this study we examined subtypes A1, A2 and B1 for this interaction. GAG-dependent infectivity of available hMPV strains was demonstrated using GAG-deficient cells and heparin competition. We expressed the G protein ectodomains from all strains and analysed these by heparin affinity chromatography. In contrast to the B2 lineage, neither the A2 or B1 G proteins bound to heparin. Sequence analysis of these strains indicated that although there was some homology with the B2 heparin-binding domains, there were less positively charged residues, providing a likely explanation for the lack of binding. Although sequence analysis did not demonstrate well defined positively charged domains in G protein of the A1 strain, this protein was able to bind heparin, albeit with a lower affinity than G protein of the B2 strain. These results indicate diversity in GAG interactions between G proteins of different lineages and suggest that the GAG-dependency of all strains may be mediated by interaction with an alternative surface protein, most probably the conserved fusion (F) protein. Analysis of both native and recombinant F protein confirmed that F protein binds heparin, supporting this conclusion. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessArticle

Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012)

by Sumana Fathima, Bonita E. Lee, Jennifer May-Hadford, Shamir Mukhi and Steven J. Drews

Viruses 2012, 4(11), 2754-2765; https://doi.org/10.3390/v4112754 - 5 Nov 2012

Cited by 14 | Viewed by 6650

Abstract

We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, [...] Read more.

We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p < 0.05]. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessArticle

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

by Luiz Gustavo Araujo Gardinassi, Paulo Vitor Marques Simas, Deriane Elias Gomes, Caroline Measso do Bonfim, Felipe Cavassan Nogueira, Gustavo Rocha Garcia, Claudia Márcia Aparecida Carareto, Paula Rahal and Fátima Pereira de Souza

Viruses 2012, 4(11), 2432-2447; https://doi.org/10.3390/v4112432 - 24 Oct 2012

Cited by 7 | Viewed by 7143

Abstract

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto – SP, [...] Read more.

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto – SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessArticle

Perinatal Lamb Model of Respiratory Syncytial Virus (RSV) Infection

by Rachel J. Derscheid and Mark R. Ackermann

Viruses 2012, 4(10), 2359-2378; https://doi.org/10.3390/v4102359 - 23 Oct 2012

Cited by 49 | Viewed by 11551

Abstract

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes [...] Read more.

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term) lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO) oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation) and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Review

Jump to: Research

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Open AccessReview

Dendritic Cells in Human Pneumovirus and Metapneumovirus Infections

by Antonieta Guerrero-Plata

Viruses 2013, 5(6), 1553-1570; https://doi.org/10.3390/v5061553 - 20 Jun 2013

Cited by 7 | Viewed by 7874

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

RSV Fusion: Time for a New Model

by Peter Mastrangelo and Richard G. Hegele

Viruses 2013, 5(3), 873-885; https://doi.org/10.3390/v5030873 - 19 Mar 2013

Cited by 40 | Viewed by 11242

Abstract

In this review we propose a partially hypothetical model of respiratory syncytial virus (RSV) binding and entry to the cell that includes the recently discovered RSV receptor nucleolin, in an attempt to stimulate further inquiry in this research area. RSV binding and entry [...] Read more.

In this review we propose a partially hypothetical model of respiratory syncytial virus (RSV) binding and entry to the cell that includes the recently discovered RSV receptor nucleolin, in an attempt to stimulate further inquiry in this research area. RSV binding and entry is likely to be a two-step process, the first involving the attachment of the virus to the cell membrane, which may be enhanced by electrostatic interactions with cellular glycoproteins/heparin and the viral G protein, and the second involving fusion to the cell membrane mediated by the viral F protein and a specific cellular fusion receptor. With our recent discovery of nucleolin as a functional fusion receptor for RSV, comes the possibility of a number of new approaches to the development of novel strategies for RSV prophylaxis and therapy, as well as raising some new questions concerning the pathobiology of RSV infection and tropism. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Th17 Lymphocytes in Respiratory Syncytial Virus Infection

by Jonas Bystrom, Nasra Al-Adhoubi, Mohammed Al-Bogami, Ali S. Jawad and Rizgar A. Mageed

Viruses 2013, 5(3), 777-791; https://doi.org/10.3390/v5030777 - 5 Mar 2013

Cited by 65 | Viewed by 9877

Abstract

Infection by respiratory syncytial virus (RSV) affects approximately 33 million infants annually worldwide and is a major cause of hospitalizations. Helper T lymphocytes (Th) play a central role in the immune response during such infections. However, Th lymphocytes that produce interleukin 17 (IL-17), [...] Read more.

Infection by respiratory syncytial virus (RSV) affects approximately 33 million infants annually worldwide and is a major cause of hospitalizations. Helper T lymphocytes (Th) play a central role in the immune response during such infections. However, Th lymphocytes that produce interleukin 17 (IL-17), known as Th17 lymphocytes, in addition to been protective can also cause pathology that accompany this type of infection. The protective effects of Th17 is associated with better prognosis in most infected individuals but heightened Th17 responses causes inflammation and pathology in others. Studies employing animal models haves shown that activated Th17 lymphocytes recruit neutrophils and facilitate tertiary lymphoid structure development in infected lungs. However, IL-17 also inhibits the ability of CD8⁺ lymphocytes to clear viral particles and acts synergistically with the innate immune system to exacerbate inflammation. Furthermore, IL-17 enhances IL-13 production which, in turn, promotes the activation of Th2 lymphocytes and excessive mucus production. Studies of these animal models have also shown that a lack of, or inadequate, responses by the Th1 subset of T lymphocytes enhances Th17-mediated responses and that this is detrimental during RSV co-infection in experimental asthma. The available evidence, therefore, indicates that Th17 can play contradictory roles during RSV infections. The factors that determine the shift in the balance between beneficial and adverse Th17 mediated effects during RSV infection remains to be determined. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Respiratory Syncytial Virus: Current Progress in Vaccine Development

by Rajeev Rudraraju, Bart G. Jones, Robert Sealy, Sherri L. Surman and Julia L. Hurwitz

Viruses 2013, 5(2), 577-594; https://doi.org/10.3390/v5020577 - 5 Feb 2013

Cited by 43 | Viewed by 9436

Abstract

Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding [...] Read more.

Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding that re-infection risks are inversely associated with neutralizing antibody titers suggest that immune responses generated toward a first RSV exposure can significantly reduce morbidity and mortality throughout life. For more than half a century, researchers have endeavored to design a vaccine for RSV that can mimic or improve upon natural protective immunity without adverse events. The virus is herein described together with the hurdles that must be overcome to develop a vaccine and some current vaccine development approaches. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Apoptosis in Pneumovirus Infection

by Elske Van den Berg, Job B.M. Van Woensel and Reinout A. Bem

Viruses 2013, 5(1), 406-422; https://doi.org/10.3390/v5010406 - 23 Jan 2013

Cited by 14 | Viewed by 9571

Abstract

Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung [...] Read more.

Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages) during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Breaking In: Human Metapneumovirus Fusion and Entry

by Reagan G. Cox and John V. Williams

Viruses 2013, 5(1), 192-210; https://doi.org/10.3390/v5010192 - 16 Jan 2013

Cited by 25 | Viewed by 11769

Abstract

Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is initiated by viral surface glycoproteins that attach to cellular receptors and mediate virus membrane fusion with cellular membranes. Most paramyxoviruses [...] Read more.

Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is initiated by viral surface glycoproteins that attach to cellular receptors and mediate virus membrane fusion with cellular membranes. Most paramyxoviruses use two viral glycoproteins to facilitate virus entry—an attachment protein and a fusion (F) protein. However, membrane fusion for the human paramyxoviruses in the Pneumovirus subfamily, HMPV and respiratory syncytial virus (hRSV), is unique in that the F protein drives fusion in the absence of a separate viral attachment protein. Thus, pneumovirus F proteins can perform the necessary functions for virus entry, i.e., attachment and fusion. In this review, we discuss recent advances in the understanding of how HMPV F mediates both attachment and fusion. We review the requirements for HMPV viral surface glycoproteins during entry and infection, and review the identification of cellular receptors for HMPV F. We also review our current understanding of how HMPV F mediates fusion, concentrating on structural regions of the protein that appear to be critical for membrane fusion activity. Finally, we illuminate key unanswered questions and suggest how further studies can elucidate how this clinically important paramyxovirus fusion protein may have evolved to initiate infection by a unique mechanism. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Human Metapneumovirus in Adults

by Lenneke E. M. Haas, Steven F. T. Thijsen, Leontine Van Elden and Karen A. Heemstra

Viruses 2013, 5(1), 87-110; https://doi.org/10.3390/v5010087 - 8 Jan 2013

Cited by 68 | Viewed by 12082

Abstract

Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than [...] Read more.

Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

by Randy E. Sacco, Jodi L. McGill, Mitchell V. Palmer, John D. Lippolis, Timothy A. Reinhardt and Brian J. Nonnecke

Viruses 2012, 4(12), 3731-3753; https://doi.org/10.3390/v4123731 - 13 Dec 2012

Cited by 23 | Viewed by 11549

Abstract

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves [...] Read more.

Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8). This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D₃. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Human Metapneumovirus Antagonism of Innate Immune Responses

by Deepthi Kolli, Xiaoyong Bao and Antonella Casola

Viruses 2012, 4(12), 3551-3571; https://doi.org/10.3390/v4123551 - 7 Dec 2012

Cited by 20 | Viewed by 9349

Abstract

Human metapneumovirus (hMPV) is a recently identified RNA virusbelonging to the Paramyxoviridae family, which includes severalmajor human and animal pathogens. Epidemiologicalstudies indicate that hMPV is a significant humanrespiratory pathogen with worldwide distribution. It is associated with respiratory illnesses in [...] Read more.

Human metapneumovirus (hMPV) is a recently identified RNA virusbelonging to the Paramyxoviridae family, which includes severalmajor human and animal pathogens. Epidemiologicalstudies indicate that hMPV is a significant humanrespiratory 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. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

The Pneumonia Virus of Mice (PVM) Model of Acute Respiratory Infection

by Kimberly D. Dyer, Katia E. Garcia-Crespo, Stephanie Glineur, Joseph B. Domachowske and Helene F. Rosenberg

Viruses 2012, 4(12), 3494-3510; https://doi.org/10.3390/v4123494 - 5 Dec 2012

Cited by 36 | Viewed by 9900

Abstract

Pneumonia Virus of Mice (PVM) is related to the human and bovine respiratory syncytial virus (RSV) pathogens, and has been used to study respiratory virus replication and the ensuing inflammatory response as a component of a natural host—pathogen relationship. As such, PVM infection [...] Read more.

Pneumonia Virus of Mice (PVM) is related to the human and bovine respiratory syncytial virus (RSV) pathogens, and has been used to study respiratory virus replication and the ensuing inflammatory response as a component of a natural host—pathogen relationship. As such, PVM infection in mice reproduces many of the clinical and pathologic features of the more severe forms of RSV infection in human infants. Here we review some of the most recent findings on the basic biology of PVM infection and its use as a model of disease, most notably for explorations of virus infection and allergic airways disease, for vaccine evaluation, and for the development of immunomodulatory strategies for acute respiratory virus infection. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Epidemiology, Molecular Epidemiology and Evolution of Bovine Respiratory Syncytial Virus

by Rosa Elena Sarmiento-Silva, Yuko Nakamura-Lopez and Gilberto Vaughan

Viruses 2012, 4(12), 3452-3467; https://doi.org/10.3390/v4123452 - 30 Nov 2012

Cited by 30 | Viewed by 9793

Abstract

The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis [...] Read more.

The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis of BRSV infection was originally hampered by its characteristic lability and poor growth in vitro. However, the advent of numerous immunological and molecular methods has facilitated the study of BRSV enormously. The knowledge gained from these studies has also provided the opportunity to develop safe, stable, attenuated virus vaccine candidates. Nonetheless, many aspects of the epidemiology, molecular epidemiology and evolution of the virus are still not fully understood. The natural course of infection is rather complex and further complicates diagnosis, treatment and the implementation of preventive measures aimed to control the disease. Therefore, understanding the mechanisms by which BRSV is able to establish infection is needed to prevent viral and disease spread. This review discusses important information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessReview

Respiratory Syncytial Virus Persistence in Macrophages Alters the Profile of Cellular Gene Expression

by Evelyn Rivera-Toledo and Beatríz Gómez

Viruses 2012, 4(12), 3270-3280; https://doi.org/10.3390/v4123270 - 22 Nov 2012

Cited by 20 | Viewed by 6808

Abstract

Viruses can persistently infect differentiated cells through regulation of expression of both their own genes and those of the host cell, thereby evading detection by the host’s immune system and achieving residence in a non-lytic state. Models in vitro with cell lines are [...] Read more.

Viruses can persistently infect differentiated cells through regulation of expression of both their own genes and those of the host cell, thereby evading detection by the host’s immune system and achieving residence in a non-lytic state. Models in vitro with cell lines are useful tools in understanding the mechanisms associated with the establishment of viral persistence. In particular, a model to study respiratory syncytial virus (RSV) persistence in a murine macrophage-like cell line has been established. Compared to non-infected macrophages, macrophages persistently infected with RSV show altered expression both of genes coding for cytokines and trans-membrane proteins associated with antigen uptake and of genes related to cell survival. The biological changes associated with altered gene expression in macrophages as a consequence of persistent RSV infection are summarized. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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