PMC:4801059 / 22338-26606
Annnotations
MyTest
{"project":"MyTest","denotations":[{"id":"26884414-23882016-29787886","span":{"begin":662,"end":664},"obj":"23882016"},{"id":"26884414-25135685-29787887","span":{"begin":666,"end":668},"obj":"25135685"},{"id":"26884414-25629011-29787888","span":{"begin":852,"end":854},"obj":"25629011"},{"id":"26884414-22174882-29787889","span":{"begin":856,"end":858},"obj":"22174882"},{"id":"26884414-6265368-29787924","span":{"begin":1186,"end":1188},"obj":"6265368"},{"id":"26884414-12660947-29787925","span":{"begin":1354,"end":1356},"obj":"12660947"},{"id":"26884414-15962219-29787926","span":{"begin":1358,"end":1360},"obj":"15962219"},{"id":"26884414-19392624-29787927","span":{"begin":1592,"end":1594},"obj":"19392624"},{"id":"26884414-18462578-29787928","span":{"begin":1829,"end":1831},"obj":"18462578"},{"id":"26884414-23028967-29787929","span":{"begin":2001,"end":2003},"obj":"23028967"},{"id":"26884414-16439519-29787930","span":{"begin":2445,"end":2448},"obj":"16439519"},{"id":"26884414-21933918-29787931","span":{"begin":2661,"end":2663},"obj":"21933918"},{"id":"26884414-2143751-29787932","span":{"begin":2847,"end":2850},"obj":"2143751"},{"id":"26884414-19487810-29787933","span":{"begin":2959,"end":2962},"obj":"19487810"},{"id":"26884414-18227219-29787934","span":{"begin":3015,"end":3018},"obj":"18227219"},{"id":"26884414-25723597-29787935","span":{"begin":3158,"end":3160},"obj":"25723597"},{"id":"26884414-16847087-29787936","span":{"begin":3177,"end":3178},"obj":"16847087"},{"id":"26884414-26172429-29787937","span":{"begin":3340,"end":3341},"obj":"26172429"},{"id":"26884414-23326226-29787938","span":{"begin":3968,"end":3970},"obj":"23326226"},{"id":"26884414-23082199-29787939","span":{"begin":3972,"end":3974},"obj":"23082199"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"MECHANISMS OF INTERACTION SUGGEST THAT VIRUS CAN ALTER BACTERIAL SELECTION IN THE LRT\nThere are several studies that support our second hypothesis, that respiratory viruses can promote bacterial colonization of the LRT by certain commensals in the URT. Viruses interact with bacteria and the host at various stages along the pathologic pathway to promote bacterial pneumonia (Table 3). For example, virus can increase shedding of URT bacteria into the LRT: in vitro biofilm and murine studies suggest influenza A virus infection can lead to the dispersion of S. pneumoniae biofilms, releasing virulent pneumococci for subsequent secondary infections in the LRT [88, 89]. When in a biofilm, S. pneumoniae is less virulent; capsule polysaccharide and pneumolysin production are reduced and synthesis of the bacterial adhesin phosphorylcholine increased [90, 91].\nTable 3 Mechanisms of synergistic virus-bacteria Interaction Abbreviations: ADV (adenovirus), IAV (influenza A virus), hMPV (human metapneumovirus), NTHi (nontypeable H. influenzae), PIV (parainfluenza virus), and RSV (respiratory syncytial virus). Viral infections also can promote bacterial adhesion to host cells [92–94]. Influenza and PIV promote bacterial adhesion with respiratory epithelium cells by cleaving sialic acid and exposing receptors on host cell oligosaccharide chains [95, 96]. In vitro and in vivo experiments suggest free sialic acid released by viral neuraminidase can behave as signaling molecules promoting pneumococcal biofilm formation, nasopharyngeal colonization and bacterial spread to the lungs [97]. Free sialic acid is believed to play a role in invasion by nontypeable H. influenza as it is an important component of the biofilm matrix and incorporated into the bacterial capsular polysaccharide to evade host defense mechanisms [98]. Although literature is scarce, the relationship may be bilateral as bacterial neuraminidase can promote virus survival during treatment with neuraminidase inhibitors [99]. In addition, viruses can promote bacterial adhesion by upregulating cell surface receptors for pathogenic bacteria. For example, RSV and PIV-3 infection can lead to upregulation of receptors intracellular adhesion molecule 1 (ICAM-1), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and platelet-activating factor receptor (PAF-r) to promote binding of nontypeable H. influenzae and S. pneumoniae to epithelial cells [100].\nRespiratory viral infection can damage and impede the repair of respiratory epithelial cells leading to reduced mucociliary clearance. Consequently, bacteria can more easily enter the lungs to cause pneumonia [75]. Many of the virus–bacteria interaction mechanisms involve viral compromise of the innate immune system. These include impairment and depletion of resident alveolar macrophages [101–103] and neutrophils, which are necessary for bacterial clearance, mediated by induction of type I interferons [104] and desensitization to Toll-like receptor ligands [105]. Detailed descriptions of potential biological pathways involved in these mechanisms are discussed in earlier reviews by Robinson et al. [55] and McCullers [9]. Finally, excessive inflammation in the lungs due to virus-initiated exacerbation of inflammatory mediators, cytokines and chemokines, can cause tissue damage [6], which increases susceptibility to secondary bacterial infections.\nDespite the considerable literature on potential mechanisms of viral–bacterial interactions that may lead to pneumonia, most studies are limited to experiments conducted in animal models using select viral and bacterial strains, which may not reflect what is occurring in human populations. Furthermore, the interactions between virus and bacteria are undoubtedly far more complex than identified in animal models, and likely consists of a complex web of interactions between different viruses and bacteria with viruses similar to that described in the URT [12, 26]. Even after considering these limitations, the overwhelming evidence for the existence of multiple biological mechanisms under various conditions supports our second hypothesis that respiratory viruses can alter bacterial selection in the LRT and is an important factor in pneumonia etiology."}
2_test
{"project":"2_test","denotations":[{"id":"26884414-23882016-29787886","span":{"begin":662,"end":664},"obj":"23882016"},{"id":"26884414-25135685-29787887","span":{"begin":666,"end":668},"obj":"25135685"},{"id":"26884414-25629011-29787888","span":{"begin":852,"end":854},"obj":"25629011"},{"id":"26884414-22174882-29787889","span":{"begin":856,"end":858},"obj":"22174882"},{"id":"26884414-6265368-29787924","span":{"begin":1186,"end":1188},"obj":"6265368"},{"id":"26884414-12660947-29787925","span":{"begin":1354,"end":1356},"obj":"12660947"},{"id":"26884414-15962219-29787926","span":{"begin":1358,"end":1360},"obj":"15962219"},{"id":"26884414-19392624-29787927","span":{"begin":1592,"end":1594},"obj":"19392624"},{"id":"26884414-18462578-29787928","span":{"begin":1829,"end":1831},"obj":"18462578"},{"id":"26884414-23028967-29787929","span":{"begin":2001,"end":2003},"obj":"23028967"},{"id":"26884414-16439519-29787930","span":{"begin":2445,"end":2448},"obj":"16439519"},{"id":"26884414-21933918-29787931","span":{"begin":2661,"end":2663},"obj":"21933918"},{"id":"26884414-2143751-29787932","span":{"begin":2847,"end":2850},"obj":"2143751"},{"id":"26884414-19487810-29787933","span":{"begin":2959,"end":2962},"obj":"19487810"},{"id":"26884414-18227219-29787934","span":{"begin":3015,"end":3018},"obj":"18227219"},{"id":"26884414-25723597-29787935","span":{"begin":3158,"end":3160},"obj":"25723597"},{"id":"26884414-16847087-29787936","span":{"begin":3177,"end":3178},"obj":"16847087"},{"id":"26884414-26172429-29787937","span":{"begin":3340,"end":3341},"obj":"26172429"},{"id":"26884414-23326226-29787938","span":{"begin":3968,"end":3970},"obj":"23326226"},{"id":"26884414-23082199-29787939","span":{"begin":3972,"end":3974},"obj":"23082199"}],"text":"MECHANISMS OF INTERACTION SUGGEST THAT VIRUS CAN ALTER BACTERIAL SELECTION IN THE LRT\nThere are several studies that support our second hypothesis, that respiratory viruses can promote bacterial colonization of the LRT by certain commensals in the URT. Viruses interact with bacteria and the host at various stages along the pathologic pathway to promote bacterial pneumonia (Table 3). For example, virus can increase shedding of URT bacteria into the LRT: in vitro biofilm and murine studies suggest influenza A virus infection can lead to the dispersion of S. pneumoniae biofilms, releasing virulent pneumococci for subsequent secondary infections in the LRT [88, 89]. When in a biofilm, S. pneumoniae is less virulent; capsule polysaccharide and pneumolysin production are reduced and synthesis of the bacterial adhesin phosphorylcholine increased [90, 91].\nTable 3 Mechanisms of synergistic virus-bacteria Interaction Abbreviations: ADV (adenovirus), IAV (influenza A virus), hMPV (human metapneumovirus), NTHi (nontypeable H. influenzae), PIV (parainfluenza virus), and RSV (respiratory syncytial virus). Viral infections also can promote bacterial adhesion to host cells [92–94]. Influenza and PIV promote bacterial adhesion with respiratory epithelium cells by cleaving sialic acid and exposing receptors on host cell oligosaccharide chains [95, 96]. In vitro and in vivo experiments suggest free sialic acid released by viral neuraminidase can behave as signaling molecules promoting pneumococcal biofilm formation, nasopharyngeal colonization and bacterial spread to the lungs [97]. Free sialic acid is believed to play a role in invasion by nontypeable H. influenza as it is an important component of the biofilm matrix and incorporated into the bacterial capsular polysaccharide to evade host defense mechanisms [98]. Although literature is scarce, the relationship may be bilateral as bacterial neuraminidase can promote virus survival during treatment with neuraminidase inhibitors [99]. In addition, viruses can promote bacterial adhesion by upregulating cell surface receptors for pathogenic bacteria. For example, RSV and PIV-3 infection can lead to upregulation of receptors intracellular adhesion molecule 1 (ICAM-1), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and platelet-activating factor receptor (PAF-r) to promote binding of nontypeable H. influenzae and S. pneumoniae to epithelial cells [100].\nRespiratory viral infection can damage and impede the repair of respiratory epithelial cells leading to reduced mucociliary clearance. Consequently, bacteria can more easily enter the lungs to cause pneumonia [75]. Many of the virus–bacteria interaction mechanisms involve viral compromise of the innate immune system. These include impairment and depletion of resident alveolar macrophages [101–103] and neutrophils, which are necessary for bacterial clearance, mediated by induction of type I interferons [104] and desensitization to Toll-like receptor ligands [105]. Detailed descriptions of potential biological pathways involved in these mechanisms are discussed in earlier reviews by Robinson et al. [55] and McCullers [9]. Finally, excessive inflammation in the lungs due to virus-initiated exacerbation of inflammatory mediators, cytokines and chemokines, can cause tissue damage [6], which increases susceptibility to secondary bacterial infections.\nDespite the considerable literature on potential mechanisms of viral–bacterial interactions that may lead to pneumonia, most studies are limited to experiments conducted in animal models using select viral and bacterial strains, which may not reflect what is occurring in human populations. Furthermore, the interactions between virus and bacteria are undoubtedly far more complex than identified in animal models, and likely consists of a complex web of interactions between different viruses and bacteria with viruses similar to that described in the URT [12, 26]. Even after considering these limitations, the overwhelming evidence for the existence of multiple biological mechanisms under various conditions supports our second hypothesis that respiratory viruses can alter bacterial selection in the LRT and is an important factor in pneumonia etiology."}