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Interferon-induced ISG15 pathway: an ongoing virus-host battle.

ABSTRACT: ISG15 is an interferon (IFN)-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by IFN. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. In this review, we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The countermeasure by influenza B virus is unique in that it exhibits species specificity. Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans.

SUBMITTER: Zhao C

PROVIDER: S-EPMC3622817 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Interferon-induced ISG15 pathway: an ongoing virus-host battle.

Zhao Chen C Collins Mark N MN Hsiang Tien-Ying TY Krug Robert M RM

Trends in microbiology 20130214 4

ISG15 is an interferon (IFN)-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by IFN. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. In this review, we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The count ...[more]

PMID: 23414970

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Project description:Alpha interferon (IFN-α) induces the transfer of resistance to hepatitis B virus (HBV) from liver nonparenchymal cells (LNPCs) to hepatocytes via exosomes. However, little is known about the entry machinery and pathway involved in the transmission of IFN-α-induced antiviral activity. In this study, we found that macrophage exosomes uniquely depend on T cell immunoglobulin and mucin receptor 1 (TIM-1), a hepatitis A virus (HAV) receptor, to enter hepatocytes for delivering IFN-α-induced anti-HBV activity. Moreover, two primary endocytic routes for virus infection, clathrin-mediated endocytosis (CME) and macropinocytosis, collaborate to permit exosome entry and anti-HBV activity transfer. Subsequently, lysobisphosphatidic acid (LBPA), an anionic lipid closely related to endosome penetration of virus, facilitates membrane fusion of exosomes in late endosomes/multivesicular bodies (LEs/MVBs) and the accompanying exosomal cargo uncoating. Together, our findings provide comprehensive insights into the transmission route of macrophage exosomes to efficiently deliver IFN-α-induced antiviral substances and highlight the similarities between the entry mechanisms of exosomes and virus.IMPORTANCE Our previous study showed that LNPC-derived exosomes could transmit IFN-α-induced antiviral activity to HBV replicating hepatocytes, but the concrete transmission mechanisms, which include exosome entry and exosomal cargo release, remain unclear. In this study, we found that virus entry machinery and pathway were also applied to exosome-mediated cell-to-cell antiviral activity transfer. Macrophage-derived exosomes distinctively exploit hepatitis A virus receptor for access to hepatocytes. Later, CME and macropinocytosis are utilized by exosomes, followed by exosome-endosome fusion for efficient transfer of IFN-α-induced anti-HBV activity. We believe that understanding the cellular entry pathway of exosomes will be beneficial to designing exosomes as efficient vehicles for antiviral therapy.

Dataset Information

Interferon-induced ISG15 pathway: an ongoing virus-host battle.

Publications

Interferon-induced ISG15 pathway: an ongoing virus-host battle.

Similar Datasets

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