The regulation of autophagy by influenza A virus

Abstract

Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality. It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection. Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules. Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host. Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus. On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg) and signaling pathways. In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis. Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains. This review discusses the regulation of autophagy, an influenza A virus driven process.

Figure 1

Autophagy machinery in infected cell. An isolation membrane initially forms around the targeting viruses or macromolecules. It is considered that this isolation membrane originates from the endoplasmic reticulum (ER), and its formation is modulated by PI3K complex which is comprised of Vps34, p150, and Beclin-1. The elongation and closure of the autophagosomes are relevant to two ubiquitin-like systems: the Atg12-Atg5-Atg16L1 and LC3-II protein conjugations. After enwrapping the autophagic cargos, the autophagosome fuses with the lysosome, resulting in the acidification of autolysosome which is concomitant with degradation of the inner autophagosome membrane and the autophagosomal contents by lysosomal hydrolysis. The viral proteins of influenza A virus induce both positive and negative regulation of the autophagy pathway.

Figure 2

The regulatory pathways of autophagy by influenza A virus.