Coxsackievirus B4 Uses Autophagy for Replication after Calpain Activation in Rat Primary Neurons

Yoon, Sun-Young; Ha, Young Eun; Choi, Jung Eun; Ahn, Jee-Yin; Lee, Heuiran; Kweon, Hee‐Seok; Lee, Jee Young; Kim, Dong Hou

doi:10.1128/jvi.01028-08

Cited by 89 publications

(89 citation statements)

References 12 publications

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“…Some pathogens induce early stages of autophagy but block later stages (i.e., autophagolysosomal fusion) (28,75,81,88,95), so we investigated whether HBV could induce a complete autophagic process (i.e., autophagic flux) by measuring the level of the autophagic substrate p62, an adaptor protein that interacts with LC3 and is specifically degraded by the autophagy pathway (4,59). The results showed that HBV could not change the expression of p62, in contrast to rapamycin ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

Liu

Wang

et al. 2011

J Virol

241

296

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Autophagy is a conserved eukaryotic mechanism that mediates the removal of long-lived cytoplasmic macromolecules and damaged organelles via a lysosomal degradative pathway. Recently, a multitude of studies have reported that viral infections may have complex interconnections with the autophagic process. The findings reported here demonstrate that hepatitis B virus (HBV) can enhance the autophagic process in hepatoma cells without promoting protein degradation by the lysosome. Mutation analysis showed that HBV small surface protein (SHBs) was required for HBV to induce autophagy. The overexpression of SHBs was sufficient to induce autophagy. Furthermore, SHBs could trigger unfolded protein responses (UPR), and the blockage of UPR signaling pathways abrogated the SHB-induced lipidation of LC3-I. Meanwhile, the role of the autophagosome in HBV replication was examined. The inhibition of autophagosome formation by the autophagy inhibitor 3-methyladenine (3-MA) or small interfering RNA duplexes targeting the genes critical for autophagosome formation (Beclin1 and ATG5 genes) markedly inhibited HBV production, and the induction of autophagy by rapamycin or starvation greatly contributed to HBV production. Furthermore, evidence was provided to suggest that the autophagy machinery was required for HBV envelopment but not for the efficiency of HBV release. Finally, SHBs partially colocalized and interacted with autophagy protein LC3. Taken together, these results suggest that the host's autophagy machinery is activated during HBV infection to enhance HBV replication.Hepatitis B virus (HBV) is a noncytopathic, enveloped DNA virus that belongs to the family Hepadnaviridae (57, 70). It is one of the most successful human pathogens, with an estimated 2 billion people infected worldwide, of whom 400 million have chronic HBV infection (54). Chronic HBV infection is correlated with a strongly increased risk for the development of liver cirrhosis and hepatocellular carcinoma (HCC) (49, 54).Effective preventive vaccines against HBV have been available for nearly three decades; however, their effectiveness in preventing blood-borne transmission from an infected mother to her newborn is about 90% (77), and therapeutic vaccines for the treatment of established hepatitis B infection are not available (65, 67). Currently, two types of antiviral therapies are approved: pegylated alpha interferon and nucleoside/nucleotide analogues (60). However, these antivirals cannot completely eradicate the virus, and their efficacy in preventing liver cirrhosis and HCC is limited (21, 64). Thus, the details of the host-virus relationship during HBV infection urgently need to be further clarified to facilitate the development of efficient therapeutic strategies for the control of HBV infection.Autophagy, an evolutionarily conserved intracellular process, involves the formation of a double membrane structure, called the autophagosome, which engulfs long-lived cytoplasmic macromolecules and damaged organelles and delivers them to lysosomes for degrada...

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Section: Resultsmentioning

confidence: 99%

“…Autophagy can contribute to innate and adaptive immunity against intracellular microbial pathogens (11, 43). However, this intracellular process has been exploited by some viruses to benefit their replication, such as poliovirus, coxsackievirus, dengue virus, hepatitis C virus, human immunodeficiency virus, and influenza A virus (14,28,42,44,75,80,95,100).…”

mentioning

confidence: 99%

Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

Liu

Wang

et al. 2011

J Virol

241

296

View full text Add to dashboard Cite

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“…Infection by poliovirus stimulates LC3 activation and autophagosome formation by a mechanism that involves the direct effects of viral nonstructural proteins (16,37); inhibition of autophagy interferes with poliovirus replication and replication of other enteroviruses in vitro (16,(38)(39)(40), and autophagy is involved in the pathogenesis of coxsackievirus-induced pancreatitis in vivo (41). Another picornavirus, foot-and-mouth disease virus (FMDV), stimulates autophagosome formation early in infection, before viral nonstructural proteins are synthesized, and FMDV colocalizes with LC3, presumably in autophagosomes, within 2 h of infection (42).…”

Section: Discussionmentioning

confidence: 99%

Echovirus 7 Entry into Polarized Caco-2 Intestinal Epithelial Cells Involves Core Components of the Autophagy Machinery

Kim

Bergelson

2014

J Virol

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bEchovirus 7 enters polarized Caco-2 intestinal epithelial cells by a clathrin-mediated endocytic process and then moves through the endosomal system before releasing its genome into the cytoplasm. We examined the possible role in virus entry of core components of the autophagy machinery. We found that depletion of Beclin-1, Atg12, Atg14, Atg16, or LC3 with specific small interfering RNAs inhibited echovirus 7 infection upstream of uncoating but had little or no effect on virus attachment to the cell surface. These data indicate that multiple autophagy-related proteins are important for one or more events that occur after the virus has bound its receptor on the cell surface but before RNA is released from the virus capsid. Although we have not determined the mechanism by which each protein contributes to virus entry, we found that stable depletion of Atg16L1 interfered with virus internalization from the cell surface rather than with intracellular trafficking. Autophagy gene products may thus participate in the endocytic process that moves virus into polarized Caco-2 cells.

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“…It has been hypothesized that this is achieved by increasing a protein-activated signaling cascade, known as the calpain-dependent pathway [45] .…”

Section: Pathogen Adaptations To Host Cell Autophagymentioning

confidence: 99%

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Sahu¹,

Ter²

2018

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In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with inflammatory pathways in the context of neuro-infections. Intracellular pathogens might have an ability to manipulate the autophagy regulation process. An augmented autophagy and inflammation at the site of infection is traditionally considered host protective. Moreover, host cell autophagy might also facilitate pathogen survivability and multiplication in the brain environment. Consequently, an excessive autophagy and neuroinflammatory process do put surrounding healthy brain tissue at risk of pathogen invasion. The question arises, whether there are any known direct interactions of intracellular neurotropic pathogens with this degradative pathway that favour intracerebral pathogen survival and growth? It is worth exploring any such cooperation between pathogen factors and altered immune pathways that modulate autophagy regulatory genes causing massive neuronal damage. A detailed understanding of molecular mechanisms in microbial pathogenesis, neuroinflammatory and neuronal autophagy pathways might identify novel therapeutic targets and diagnostic biomarkers.

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Coxsackievirus B4 Uses Autophagy for Replication after Calpain Activation in Rat Primary Neurons

Cited by 89 publications

References 12 publications

Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

Subversion of Cellular Autophagy Machinery by Hepatitis B Virus for Viral Envelopment

Echovirus 7 Entry into Polarized Caco-2 Intestinal Epithelial Cells Involves Core Components of the Autophagy Machinery

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

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