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Respiratory viral infections and host responses; insights from genomics.

ABSTRACT: Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the molecular networks that differentiate symptomatic from asymptomatic respiratory viral infections, and identify the underlying molecular drivers of these networks. Finally, we discuss unique aspects of the biology and pathogenesis of infections with respiratory syncytial virus, rhinovirus and influenza, drawing on insights from genomics.

SUBMITTER: Troy NM

PROVIDER: S-EPMC5117516 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Respiratory viral infections and host responses; insights from genomics.

Troy Niamh M NM Bosco Anthony A

Respiratory research 20161121 1

Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the molecular networks that differentiate symptomatic from asymptomatic respiratory viral infections, and identify the unde ...[more]

PMID: 27871304

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Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. Healthy adults were invited to enroll to be followed for acute respiratory illness (ARI) through two consecutive influenza seasons 2009-2010 and 2010-2011. After subjects provided consent, baseline blood specimens were obtained during enrollment. Subjects were given thermometers and instructions to call and report for evaluation within 48 hours of ARI onset. Those persons who had a new ARI were seen within 48 hours of onset (day 0) and 2, 4, and 6 days later for repeat evaluation, blood specimen collections, and medical care (including the antiviral zanamivir if indicated) and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection by RT-PCR on day 0 and day 2. Surveillance for influenza was terminated after 5.5 months; all subjects were asked to return for specimen collection and to provide a medical and ARI history in spring of next year. Serum specimens obtained at baseline, day 0 and day 21 visits for illnesses, and the terminal visit were tested simultaneously using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains. Peripheral blood RNA (PaxGene) obtained from blood specimens at each visit were analyzed using Illumina Human HT-12 v4. The study was repeated 2010-2011. A total of 880 arrays, corresponding to 133 individuals, passed quality control and are included in this data set.

Project description:With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13-31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential.The reviews of this paper are available via the supplemental material section.

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Respiratory viral infections and host responses; insights from genomics.

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Respiratory viral infections and host responses; insights from genomics.

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