Influenza A Virus Infection, Innate Immunity, and Childhood

Abstract

Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population.Influenza A virus (IAV) is a highly contagious RNA virus that causes respiratory tract infections in humans and animals. Seasonal IAV is responsible for considerable disease worldwide, with the World Health Organization estimating 3 to 5 million severe cases of IAV each year and approximately 250 000 to 500 000 deaths. 1 Pandemics threaten to affect significantly more people. During the 1918 pandemic, it is estimated that IAV was responsible for 50 to 100 million deaths. 2 The burden of IAV infection is highest in children, the elderly, and persons with chronic medical conditions. Each year, IAV infection affects up to 40% of children younger than 5 years in the United States and 90 million

Differentially expressed non-coding RNAs induced by transmissible gastroenteritis virus potentially regulate inflammation and NF-κB pathway in porcine intestinal epithelial cell line

“…TLR3, a member of TLR family, has a fundamental role in recognizing dsRNA of viruses and activation of IRF3 and NF-κB pathway [31]. In addition, other viruses, such as PSV and Influenza A virus, also give rise to activation of NF-κB pathway via recognition of viral RNA by TLR3 [32,33]. Consistently, we find TGEV infection upregulates RIG-I and TLR3 and induces the activation of NF-κB pathway in IPEC-J2 cells, indicating TGEV may activate NF-κB pathway via RIG-I and TLR3 signaling.…”

Potent Protection Against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting

“…A basic principle of flu epidemiology is that children under 5 and elderly adults over 65 are high-risk groups for influenza infection (42)(43)(44) . These groups may be more susceptible to severe influenza infections, or may seek healthcare at an increased rate, leading to caseascertainment biases.…”

“…A well-established pattern in influenza epidemiology is that young children and the elderly are at elevated risk for hospitalization and severe disease (42)(43)(44). Thus we designed our family of multinomial models to allow for elevated risk of severe disease in each of these age groups, via the parameters A c and A e respectively, to ensure that we accounted for all known age-related effects before testing our hypothesis of HA imprinting.…”

Human genetics of life-threatening influenza pneumonitis

“…Both IAV and IBV are negative-sense ssRNA viruses in the Orthomyxoviridae virus family. Influenza affects 5-10% of adults and up to 40% of children under the age of 5 years every year in the USA (World Health Organization 2014; Molinari et al 2007;Coates et al 2015). The influenza virus usually causes a relatively mild disease of the upper respiratory tract that is readily cleared with little need for medical intervention (Kuiken et al 2012).…”