Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses

Sandt, Carolien E. van de; Kreijtz, Joost H. C. M.; Rimmelzwaan, Guus F.

doi:10.3390/v4091438

Cited by 185 publications

(188 citation statements)

References 321 publications

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“…Subsequent binding of type I IFNs to their cognate receptor leads to the activation of the JAK/STAT pathway, generating a positive-feedback loop that prolongs activation of IFN-stimulated genes, mediates a second wave of IFN secretion, and leads to the production of antiviral proteins such as ISG56/IFIT1 and STAT2 (15,16). The success of IAV depends on its capacity to either subvert or subdue the host immune response for a productive replication (13,17). As such, it encodes several virulence factors that inhibit type I IFN signaling and/or promote viral-induced early apoptosis of immune cells (13,18).…”

mentioning

confidence: 99%

“…Early innate antiviral immunity mainly relies on the production of type I IFN (10)(11)(12)(13)(14). Secreted type I IFNs function in an autocrine and paracrine fashion are critical for the early control of viral replication by activating the transcription of intrinsic antiviral factors.…”

mentioning

confidence: 99%

“…The success of IAV depends on its capacity to either subvert or subdue the host immune response for a productive replication (13,17). As such, it encodes several virulence factors that inhibit type I IFN signaling and/or promote viral-induced early apoptosis of immune cells (13,18).…”

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confidence: 99%

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NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein

Jaworska

François

Downey

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

114

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To subvert host immunity, influenza A virus (IAV) induces early apoptosis in innate immune cells by disrupting mitochondria membrane potential via its polymerase basic protein 1-frame 2 (PB1-F2) accessory protein. Whether immune cells have mechanisms to counteract PB1-F2-mediated apoptosis is currently unknown. Herein, we define that the host mitochondrial protein nucleotide-binding oligomerization domain-like receptor (NLR)X1 binds to viral protein PB1-F2, preventing IAV-induced macrophage apoptosis and promoting both macrophage survival and type I IFN signaling. We initially observed that Nlrx1-deficient mice infected with IAV exhibited increased pulmonary viral replication, as well as enhanced inflammatory-associated pulmonary dysfunction and morbidity. Analysis of the lungs of IAV-infected mice revealed markedly enhanced leukocyte recruitment but impaired production of type I IFN in Nlrx1 −/− mice. Impaired type I IFN production and enhanced viral replication was recapitulated in Nlrx1 −/− macrophages and was associated with increased mitochondrial mediated apoptosis. Through gain-and loss-of-function strategies for protein interaction, we identified that NLRX1 directly bound PB1-F2 in the mitochondria of macrophages. Using a recombinant virus lacking PB1-F2, we confirmed that deletion of PB1-F2 abrogated NLRX1-dependent macrophage type I IFN production and apoptosis. Thus, our results demonstrate that NLRX1 acts as a mitochondrial sentinel protecting macrophages from PB1-F2-induced apoptosis and preserving their antiviral function. We further propose that NLRX1 is critical for macrophage immunity against IAV infection by sensing the extent of viral replication and maintaining a protective balance between antiviral immunity and excessive inflammation within the lungs.innate immunity | Nod-like receptor

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confidence: 99%

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confidence: 99%

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NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein

Jaworska

François

Downey

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

114

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“…In influenza virus infections, interleukin (IL)-10 is secreted in significant amounts, along with effector inflammatory cytokines [2][3][4][5][6]19,20 . The role of IL-10 in influenza virus infections remains ambiguous.…”

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confidence: 99%

“…The clinical outcome of an infection depends primarily on the interplay between the virus and the host immune reactions to the infection. The influenza virus uses strategies to circumvent host defenses for the establishment of infection and efficient replication 1,2 . The host immune system, on the other hand, responds to limit viral spread, as well as to eradicate the virus [3][4][5][6][7][8] .…”

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confidence: 99%

IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

et al. 2015

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Influenza A Virus Infection, Innate Immunity, and Childhood

et al. 2015

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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

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Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses

Cited by 185 publications

References 321 publications

NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein

NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein

IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

Influenza A Virus Infection, Innate Immunity, and Childhood

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