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Viruses Jun 2019Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one... (Review)
Review
Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection's epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.
Topics: Adaptive Immunity; Antiviral Agents; Asthma; Bronchiolitis; Child; Child Health; Humans; Immunity, Cellular; Infant; Inflammation; Picornaviridae Infections; Respiratory Hypersensitivity; Respiratory Sounds; Rhinovirus; Serogroup; Viral Vaccines
PubMed: 31195744
DOI: 10.3390/v11060521 -
Clinical Microbiology Reviews Jan 2013Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical... (Review)
Review
Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs.
Topics: Genetic Variation; Genotype; Humans; Otitis Media; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus; Sinusitis
PubMed: 23297263
DOI: 10.1128/CMR.00077-12 -
Viruses Apr 2021Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to... (Review)
Review
Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to cause severe disease and exacerbations in asthma and COPD patients. Viruses being obligate parasites, hijack host cell pathways such as programmed cell death to suppress host antiviral responses and prolong viral replication and propagation. RVs are non-enveloped positive sense RNA viruses with a lifecycle fully contained within the cytoplasm. Despite decades of study, the details of how RVs exit the infected cell are still unclear. There are some diverse studies that suggest a possible role for programmed cell death. In this review, we aimed to consolidate current literature on the impact of RVs on cell death to inform future research on the topic. We searched peer reviewed English language literature in the past 21 years for studies on the interaction with and modulation of cell death pathways by RVs, placing it in the context of the broader knowledge of these interconnected pathways from other systems. Our review strongly suggests a role for necroptosis and/or autophagy in RV release, with the caveat that all the literature is based on RV-A and RV-B strains, with no studies to date examining the interaction of RV-C strains with cell death pathways.
Topics: Autophagy; Cell Death; Humans; Necroptosis; Picornaviridae Infections; Rhinovirus; Virus Replication
PubMed: 33916958
DOI: 10.3390/v13040629 -
Chest May 2019Human rhinoviruses (RVs) are picornaviruses that can cause a variety of upper and lower respiratory tract illnesses, including the common cold, bronchitis, pneumonia,... (Review)
Review
Human rhinoviruses (RVs) are picornaviruses that can cause a variety of upper and lower respiratory tract illnesses, including the common cold, bronchitis, pneumonia, and exacerbations of chronic respiratory diseases such as asthma. There are currently > 160 known types of RVs classified into three species (A, B, and C) that use three different cellular membrane glycoproteins expressed in the respiratory epithelium to enter the host cell. These viral receptors are intercellular adhesion molecule 1 (used by the majority of RV-A and all RV-B types), low-density lipoprotein receptor family members (used by 12 RV-A types), and cadherin-related family member 3 (CDHR3; used by RV-C). RV-A and RV-B interactions with intercellular adhesion molecule 1 and low-density lipoprotein receptor glycoproteins are well defined and their cellular functions have been described, whereas the mechanisms of the RV-C interaction with CDHR3 and its cellular functions are being studied. A single nucleotide polymorphism (rs6967330) in CDHR3 increases cell surface expression of this protein and, as a result, also promotes RV-C infections and illnesses. There are currently no approved vaccines or antiviral therapies available to treat or prevent RV infections, which is a major unmet medical need. Understanding interactions between RV and cellular receptors could lead to new insights into the pathogenesis of respiratory illnesses as well as lead to new approaches to control respiratory illnesses caused by RV infections.
Topics: Host Microbial Interactions; Humans; Picornaviridae Infections; Receptors, Virus; Rhinovirus
PubMed: 30659817
DOI: 10.1016/j.chest.2018.12.012 -
Viruses Jan 2022Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of... (Review)
Review
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples.
Topics: Asthma; Coinfection; Enterovirus; Enterovirus Infections; Genotyping Techniques; Hospitalization; Humans; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus; Serotyping
PubMed: 35062345
DOI: 10.3390/v14010141 -
F1000Research 2018Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma,... (Review)
Review
Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma, bronchiolitis in infants, and significant lower respiratory tract infections in children, the immunosuppressed, and the elderly. The large number of rhinovirus strains (currently about 160) and their antigenic diversity are significant obstacles in vaccine development. The phenotype of immune responses induced during rhinovirus infection can affect disease severity. Recognition of rhinovirus and a balance of innate responses are important factors in rhinovirus-induced morbidity. Immune responses to rhinovirus infections in healthy individuals are typically of the T helper type 1 (Th1) phenotype. However, rhinovirus-driven asthma exacerbations are additionally characterised by an amplified Th2 immune response and airway neutrophilia. This commentary focuses on recent advances in understanding immunity toward rhinovirus infection and how innate and adaptive immune responses drive rhinovirus-induced asthma exacerbations.
Topics: Adaptive Immunity; Asthma; Humans; Immunity, Innate; Picornaviridae Infections; Rhinovirus; Th1 Cells; Th2 Cells
PubMed: 30345002
DOI: 10.12688/f1000research.15337.1 -
Journal of the Formosan Medical... Jul 2017Rhinovirus has been neglected in the past because it was generally perceived as a respiratory virus only capable of causing mild common cold. Contemporary... (Review)
Review
Rhinovirus has been neglected in the past because it was generally perceived as a respiratory virus only capable of causing mild common cold. Contemporary epidemiological studies using molecular assays have shown that rhinovirus is frequently detected in adult and pediatric patients with upper or lower respiratory tract infections. Severe pulmonary and extrapulmonary complications are increasingly recognized. Contrary to popular belief, some rhinoviruses can actually replicate well at 37 °C and infect the lower airway in humans. The increasing availability of multiplex PCR panels allows rapid detection of rhinovirus and provides the opportunity for timely treatment and early recognition of outbreaks. Recent advances in the understanding of host factors for viral attachment and replication, and the host immunological response in both asthmatic and non-asthmatic individuals, have provided important insights into rhinovirus infection which are crucial in the development of antiviral treatment. The identification of novel drugs has been accelerated by repurposing clinically-approved drugs. As humoral antibodies induced by past exposure and vaccine antigen of a particular serotype cannot provide full coverage for all rhinovirus serotypes, novel vaccination strategies are required for inducing protective response against all rhinoviruses.
Topics: Adaptive Immunity; Genome, Viral; Humans; Immunity, Innate; Picornaviridae Infections; Rhinovirus; Viral Vaccines; Virus Replication
PubMed: 28495415
DOI: 10.1016/j.jfma.2017.04.009 -
Antiviral Research Sep 2006Human rhinoviruses (HRV), members of the Picornaviridae family, are comprised of over 100 different virus serotypes. HRV represent the single most important etiological... (Review)
Review
Human rhinoviruses (HRV), members of the Picornaviridae family, are comprised of over 100 different virus serotypes. HRV represent the single most important etiological agents of the common cold [Arruda, E., Pitkaranta, A., Witek Jr., T.J., Doyle, C.A., Hayden, F.G., 1997. Frequency and natural history of rhinovirus infections in adults during autumn. J. Clin. Microbiol. 35, 2864-2868; Couch, R.B., 1990. Rhinoviruses. In: Fields, B.N., Knipe, D.M. (Eds.), Virology. Raven Press, New York, pp. 607-629; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14]. Although HRV-induced upper respiratory illness is often mild and self-limiting, the socioeconomic impact caused by missed school or work is enormous and the degree of inappropriate antibiotic use is significant. It has been estimated that upper respiratory disease accounts for at least 25 million absences from work and 23 million absences of school annually in the United States [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. Increasing evidences also describe the link between HRV infection and more serious medical complications. HRV-induced colds are the important predisposing factors to acute otitis media, sinusitis, and are the major factors in the induction of exacerbations of asthma in adults and children. HRV infections are also associated with lower respiratory tract syndromes in individuals with cystic fibrosis, bronchitis, and other underlying respiratory disorders [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gern, J.E., Busse, W.W., 1999. Association of rhinovirus infections with asthma. Clin. Microbiol. Rev. 12 (1), 9-18; Pitkaranta, A., Arruda, E., Malmberg, H., Hayden, F.G., 1997. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J. Clin. Microbiol. 35, 1791-1793; Pitkaranta, A., Virolainen, A., Jero, J., Arruda, E., Hayden, F.G., 1998. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 102, 291-295; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. To date, no effective antiviral therapies have been approved for either the prevention or treatment of diseases caused by HRV infection. Thus, there still exists a significant unmet medical need to find agents that can shorten the duration of HRV-induced illness, lessen the severity of symptoms, minimize secondary bacterial infections and exacerbations of underlying disease and reduce virus transmission. Although effective over-the-counter products have been described that alleviate symptoms associated with the common cold [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gwaltney, J.M., 2002a. Viral respiratory infection therapy: historical perspectives and current trials. Am. J. Med. 22 (112 Suppl. 6A), 33S-41S; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14; Sperber, S.J., Hayden, F.G., 1988. Chemotherapy of rhinovirus colds. Antimicrob. Agents Chemother. 32, 409-419], this review will primarily focus on the discovery and development of those agents that directly or indirectly impact virus replication specifically highlighting new advances and/or specific challenges with their development.
Topics: Antiviral Agents; Capsid; Humans; Picornaviridae Infections; Protease Inhibitors; Rhinovirus
PubMed: 16675037
DOI: 10.1016/j.antiviral.2006.03.011 -
Viruses Jun 2020Protein-shelled viruses have been thought as "tin cans" that merely carry the genomic cargo from cell to cell. However, through the years, it has become clear that... (Review)
Review
Protein-shelled viruses have been thought as "tin cans" that merely carry the genomic cargo from cell to cell. However, through the years, it has become clear that viruses such as rhinoviruses and caliciviruses are active and dynamic structures waiting for the right environmental cues to deliver their genomic payload to the host cell. In the case of human rhinoviruses, the capsid has empty cavities that decrease the energy required to cause conformational changes, resulting in the capsids "breathing", waiting for the moment when the receptor binds for it to release its genome. Most strikingly, the buried N-termini of VP1 and VP4 are transiently exposed during this process. A more recent example of a "living" protein capsid is mouse norovirus (MNV). This family of viruses have a large protruding (P) domain that is loosely attached to the shell via a single-polypeptide tether. Small molecules found in the gut, such as bile salts, cause the P domains to rotate and collapse onto the shell surface. Concomitantly, bile alters the conformation of the P domain itself from one that binds antibodies to one that recognizes receptors. In this way, MNV appears to use capsid flexibility to present one face to the immune system and a completely different one to attack the host tissue. Therefore, it appears that even protein-shelled viruses have developed an impressive array of tricks to dodge our immune system and efficiently attack the host.
Topics: Animals; Caliciviridae; Caliciviridae Infections; Capsid; Humans; Picornaviridae Infections; Rhinovirus; Viral Proteins
PubMed: 32516952
DOI: 10.3390/v12060618 -
Viruses Nov 2020Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial... (Review)
Review
Human rhinoviruses have been linked both to the susceptibility of asthma development and to the triggering of acute exacerbations. Given that the human airway epithelial cell is the primary site of human rhinovirus (HRV) infection and replication, the current review focuses on how HRV-induced modulation of several aspects of epithelial cell phenotype could contribute to the development of asthma or to the induction of exacerbations. Modification of epithelial proinflammatory and antiviral responses are considered, as are alterations in an epithelial barrier function and cell phenotype. The contributions of the epithelium to airway remodeling and to the potential modulation of immune responses are also considered. The potential interactions of each type of HRV-induced epithelial phenotypic changes with allergic sensitization and allergic phenotype are also considered in the context of asthma development and of acute exacerbations.
Topics: Asthma; Bronchi; Epithelial Cells; Humans; Phenotype; Picornaviridae Infections; Rhinovirus
PubMed: 33227953
DOI: 10.3390/v12111328