Host Mitochondrial Requirements of Cytomegalovirus Replication
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VIROLOGY (S LI AND K PARVATIYAR, SECTION EDITORS)
Host Mitochondrial Requirements of Cytomegalovirus Replication Chandler H. Monk 1 & Kevin J. Zwezdaryk 1 Accepted: 15 September 2020 # The Author(s) 2020
Abstract Purpose of Review Metabolic rewiring of the host cell is required for optimal viral replication. Human cytomegalovirus (HCMV) has been observed to manipulate numerous mitochondrial functions. In this review, we describe the strategies and targets HCMV uses to control different aspects of mitochondrial function. Recent Findings The mitochondria are instrumental in meeting the biosynthetic and bioenergetic needs of HCMV replication. This is achieved through altered metabolism and signaling pathways. Morphological changes mediated through biogenesis and fission/fusion dynamics contribute to strategies to avoid cell death, overcome oxidative stress, and maximize the biosynthetic and bioenergetic outputs of mitochondria. Summary Emerging data suggests that cytomegalovirus relies on intact, functional host mitochondria for optimal replication. HCMV large size and slow replication kinetics create a dependency on mitochondria during replication. Targeting the host mitochondria is an attractive antiviral target. Keywords Mitochondria . CMV . ETC . Membrane potential . Oxidative phosphorylation . ROS
Introduction As obligate parasites, viruses are dependent on the host for replication. By themselves, they are incapable of energy production. Key to this is a viral dependency on the host cellular metabolic network for replication. Nearly 70 years ago, it was established that many viruses including poliomyelitis virus, herpes simplex virus 1, and Rous sarcoma virus altered glycolytic pathways of infected cells [1–3]. These observations were expanded to include manipulation of adenosine triphosphate (ATP) production and RNA breakdown. Through altered host metabolism, viruses can support their mass production. This requires manipulation of host organelles and resources to reproduce viral particles. Biosynthetic (nucleotides, amino acids, lipids) and bioenergetic requirements are critical for viral replication. Many of the metabolic pathways targeted or altered during viral infection converge or are dependent on the host mitochondria. This article is part of the Topical Collection on Virology * Kevin J. Zwezdaryk [email protected] 1
Department of Microbiology & Immunology, Tulane University Health Sciences Center, 1430 Tulane Ave #8638, New Orleans, LA 70112, USA
Mitochondria have long been regarded as the powerhouse of the cell. Yet, this organelle has been shown to have essential functions in signal transduction pathways, cellular metabolism, immune response, cell cycle, and cell death (reviewed in [4]) (Fig. 1). The mitochondrion is composed of outer and inner membranes. The outer membrane surrounds the inner membrane space, an area that contains many apoptotic factors (e.g., cytochrome complex (cyt-c), endonuclease G). These factors are released by apoptotic signaling cascades received by the mitochondria. The
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