Influence of cellular lipid content on influenza A virus replication
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ORIGINAL ARTICLE
Influence of cellular lipid content on influenza A virus replication Nattavatchara Limsuwat1 · Chompunuch Boonarkart1 · Supinya Phakaratsakul1 · Ornpreya Suptawiwat2 · Prasert Auewarakul1 Received: 27 July 2019 / Accepted: 21 March 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Influenza A virus (IAV) depends on the metabolism of its cellular host to provide energy and essential factors, including lipids, for viral replication. Previous studies have shown that fatty acids (FAs) play an important role in IAV replication and that inhibition of FA biosynthesis can diminish viral replication. However, cellular lipids can either be synthesized intracellularly or be imported from the extracellular environment. Interfering with FA import mechanisms may reduce the cellular lipid content and inhibit IAV replication. To test this hypothesis, MDCK and Detroit 562 cells were infected with IAV followed by exposure to palmitic acid and inhibitors of FA import. Replication of IAV significantly increased when infected cells were supplied with palmitic acid. This enhancement could be reduced by adding an FA import inhibitor. The addition of palmitic acid significantly increased the cellular lipid content, and this increased level was reduced by treatment with an FA import inhibitor. These results show that reducing the cellular lipid level might be an approach for IAV therapy.
Introduction Influenza A virus (IAV) is an important virus that causes respiratory diseases in humans and many animal species worldwide. The IAV subtypes that have been circulating in humans are H1N1 and H3N2. In the 20th century, there were three major IAV pandemics: Spanish flu in 1918 (H1N1), Asian flu in 1957 (H2N2), Hong Kong flu in 1968 (H3N2). In 2009, WHO declared that a new strain of swine-origin H1N1, known as “swine flu”, was responsible for the first pandemic of the 21st century. The major concept of antiinfluenza drugs for humans is targeting conserved viral components that are critical for viral replication. Two types of anti-influenza drugs are commonly used, matrix protein 2 (M2) ion channel blockers and the neuraminidase inhibitors. A new class of cap-dependent endonuclease inhibitor (baloxavir marboxil) has been approved recently for treatment of Handling Editor: Ayato Takada. * Prasert Auewarakul [email protected] 1
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkok 10700, Thailand
Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
2
influenza. However, resistance to the available drugs is a major public-health concern, and development of alternative treatments is required [16, 28]. All viruses depend on cellular factors to complete their replication cycle. Among the host cell factors that are essential for viruses, cellular lipids play a key role in the viral replication cycle. Some viruses can regulate cellular metabolism of infec
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