Sex differences in antiviral immunity in SARS‐CoV‐2 infection: Mitochondria and mitomiR come into view

Mitochondria are multifaceted organelles representing the "powerhouse of cells" for their function as bioenergetics and biosynthetic hubs. In addition, they play an essential role in the regulation of innate and adaptive immune responses, including host defenses against viruses, as well as in inflammatory responses 1 . This peculiar role of mitochondria is principally due to the activation of adaptor mitochondrial proteins, known as mitochondrial antiviral signaling (MAVS) proteins. MAVS sense viral RNA and trigger the activation of the transcription factor NF-kB or IFN pathways and autophagy, in order to clear the infection and avoid excessive inflammation, respectively1 .

[1]  Keshav K. Singh,et al.  Mitochondria and microbiota dysfunction in COVID-19 pathogenesis , 2020, Mitochondrion.

[2]  M. Kloc,et al.  The Role of Genetic Sex and Mitochondria in Response to COVID-19 Infection , 2020, International Archives of Allergy and Immunology.

[3]  G. Chaubey,et al.  Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis , 2020, American journal of physiology. Cell physiology.

[4]  Benjamin J. Polacco,et al.  A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing , 2020, Nature.

[5]  P. Conti,et al.  Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection. , 2020, Journal of biological regulators and homeostatic agents.

[6]  F. Ciccosanti,et al.  Mitochondrial Interactome: A Focus on Antiviral Signaling Pathways , 2020, Frontiers in Cell and Developmental Biology.

[7]  S. Galluzzi,et al.  miR-146a Plasma Levels Are Not Altered in Alzheimer’s Disease but Correlate With Age and Illness Severity , 2020, Frontiers in Aging Neuroscience.

[8]  M. Zeng,et al.  microRNAs in viral acute respiratory infections: immune regulation, biomarkers, therapy, and vaccines , 2019, ExRNA.

[9]  Liang Zhang,et al.  MicroRNA-221-5p Inhibits Porcine Epidemic Diarrhea Virus Replication by Targeting Genomic Viral RNA and Activating the NF-κB Pathway , 2018, International journal of molecular sciences.

[10]  S. Klein,et al.  The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility , 2018, Seminars in Immunopathology.

[11]  E. Fikrig,et al.  MiR-221 negatively regulates innate anti-viral response , 2018, PloS one.

[12]  R. Klein,et al.  Sex Drives Dimorphic Immune Responses to Viral Infections , 2017, The Journal of Immunology.

[13]  Huanchun Chen,et al.  MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11 , 2016, Journal of Virology.

[14]  C. Klinge.  miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets , 2015, Molecular and Cellular Endocrinology.

[15]  Mones Abu-Asab,et al.  SARS-Coronavirus Open Reading Frame-9b Suppresses Innate Immunity by Targeting Mitochondria and the MAVS/TRAF3/TRAF6 Signalosome , 2014, The Journal of Immunology.

[16]  A. Procopio,et al.  MitomiRs in human inflamm-aging: A hypothesis involving miR-181a, miR-34a and miR-146a , 2014, Experimental Gerontology.

[17]  S. Barik,et al.  Viral degradasome hijacks mitochondria to suppress innate immunity , 2013, Cell Research.

[18]  Cheryl Walton,et al.  MicroRNA-221 Modulates RSV Replication in Human Bronchial Epithelium by Targeting NGF Expression , 2012, PloS one.

[19]  O. Crasta,et al.  Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. , 2008, Blood.