Abstract:
:Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other's spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or in vitro Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses.IMPORTANCE Viral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.
journal_name
J Viroljournal_title
Journal of virologyauthors
Gonzalez AJ,Ijezie EC,Balemba OB,Miura TAdoi
10.1128/JVI.00881-18subject
Has Abstractpub_date
2018-11-12 00:00:00issue
23eissn
0022-538Xissn
1098-5514pii
JVI.00881-18journal_volume
92pub_type
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journal_title:Journal of virology
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doi:10.1128/JVI.55.3.601-610.1985
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doi:10.1128/JVI.71.12.9743-9752.1997
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pub_type: 杂志文章
doi:10.1128/JVI.67.8.4588-4597.1993
更新日期:1993-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8446-8452.1998
更新日期:1998-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.02316-15
更新日期:2015-10-28 00:00:00
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更新日期:2014-01-01 00:00:00
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doi:10.1128/JVI.00542-19
更新日期:2019-06-28 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.3.1398-1401.1990
更新日期:1990-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.79.18.11627-11637.2005
更新日期:2005-09-01 00:00:00
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更新日期:2009-05-01 00:00:00
abstract::The human herpesvirus entry mediator C (HveC), also known as the poliovirus receptor-related protein 1 (PRR1) and as nectin-1, allows the entry of herpes simplex virus type 1 (HSV-1) and HSV-2 into mammalian cells. The interaction of virus envelope glycoprotein D (gD) with such a receptor is an essential step in the p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.10863-10872.2000
更新日期:2000-12-01 00:00:00
abstract::Virus-induced cell fusion of the fusion-from-without type was observed in SC-1 cells infected with Moloney murine leukemia virus when grown in NIH 3T3 cells. Replication-competent virus mutants with altered surface protein gp70 were examined. Fusion mutations were found in the proline-rich region of gp70. They acted o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3175-3182.1994
更新日期:1994-05-01 00:00:00
abstract::The Birnaviridae family, responsible for major economic losses to poultry and aquaculture, is composed of nonenveloped viruses with a segmented double-stranded RNA (dsRNA) genome that replicate in discrete cytoplasmic virus factories (VFs). Reassortment is common; however, the underlying mechanism remains unknown give...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02107-19
更新日期:2020-06-16 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5914-5923.1992
更新日期:1992-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.6.1367-1377.1975
更新日期:1975-06-01 00:00:00
abstract::The matrix domain of human immunodeficiency virus type 1 Gag polyprotein was studied for its role in virus assembly. Deletion and substitution mutations caused a dramatic reduction in virus production. Mutant Gag polyproteins were myristoylated and had a high affinity for membrane association. Immunofluorescence stain...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6387-6394.1993
更新日期:1993-11-01 00:00:00
abstract:UNLABELLED:The four serotypes of dengue virus (DENV) cause the most important and rapidly emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a tetravalent dengue vaccine reported a moderate efficacy despite the presence of neutralizing antibodies, highlighting the need for a better understandin...
journal_title:Journal of virology
pub_type: 杂志文章,随机对照试验
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更新日期:2015-07-01 00:00:00
abstract::In two cases of parenteral transmission of human immunodeficiency virus type 1 (HIV-1) syncitium-inducing (SI) variants, we previously observed selection for macrophagetropic variants. Although infection of macrophages is generally mediated via CCR5, we found no selection for SI variants that could use CCR5 as corecep...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.18.8848-8853.2001
更新日期:2001-09-01 00:00:00