Influenza A virus H5N1 entry into host cells is through clathrin-dependent endocytosis

Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.

Lysosome-mediated chemoresistance in acute myeloid leukemia

Despite the outstanding advances in understanding the biology underlying the pathophysiology of acute myeloid leukemia(AML)and the promising preclinical data published lastly,AML treatment still relies on a classic chemotherapy regimen largely unchanged for the past five decades.Recently,new drugs have been approved for AML,but the real clinical benefit is still under evaluation.Nevertheless,primary refractory and relapse AML continue to represent the main clinical challenge,as the majority of AML patients will succumb to the disease despite achieving a complete remission during the induction phase.As such,treatments for chemoresistant AML represent an unmet need in this disease.Although great efforts have been made to decipher the biological basis for leukemogenesis,the mechanism by which AML cells become resistant to chemotherapy is largely unknown.The identification of the signaling pathways involved in resistance may lead to new combinatory therapies or new therapeutic approaches suitable for this subset of patients.Several mechanisms of chemoresistance have been identified,including drug transporters,key secondary messengers,and metabolic regulators.However,no therapeutic approach targeting chemoresistance has succeeded in clinical trials,especially due to broad secondary effects in healthy cells.Recent research has highlighted the importance of lysosomes in this phenomenon.Lysosomes’key role in resistance to chemotherapy includes the potential to sequester drugs,central metabolic signaling role,and gene expression regulation.These results provide further evidence to support the development of new therapeutic approaches that target lysosomes in AML.