Neda Feizi1, Parvaneh Mehrbod1, Bizhan Romani2,3, Hoorieh Soleimanjahi4, Taravat Bamdad4, Amir Feizi5, Ehsan Ollah Jazaeri6, Hadiseh Shokouhi Targhi1, Maryam Saleh1, Abbas Jamali1, Fatemeh Fotouhi1, Reza Nasrollahi Nargesabad6, Asghar Abdoli6. 1. Influenza and Other Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran. 2. Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur, University of Medical Sciences (AJUMS), Ahvaz, 61357-15794, Iran. 3. Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2E1, Canada. 4. Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 5. Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 412 96 Gothenburg, Sweden. 6. Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Abstract
PURPOSE: Autophagy plays a key role in host defence responses against microbial infections by promoting degradation of pathogens and participating in acquired immunity. The interaction between autophagy and viruses is complex, and this pathway is hijacked by several viruses. Influenza virus (IV) interferes with autophagy through its replication and increases the accumulation of autophagosomes by blocking lysosome fusion. Thus, autophagy could be an effective area for antiviral research. METHODOLOGY: In this study, we evaluated the effect of autophagy on IV replication. Two cell lines were transfected with Beclin-1 expression plasmid before (prophylactic approach) and after (therapeutic approach) IV inoculation.Results/Key findings. Beclin-1 overexpression in the cells infected by virus induced autophagy to 26 %. The log10haemagglutinin titre and TCID50 (tissue culture infective dose giving 50 % infection) of replicating virus were measured at 24 and 48 h post-infection. In the prophylactic approach, the virus titre was enhanced significantly at 24 h post-infection (P≤0.01), but it was not significantly different from the control at 48 h post-infection. In contrast, the therapeutic approach of autophagy induction inhibited the virus replication at 24 and 48 h post-infection. Additionally, we showed that inhibition of autophagy using 3-methyladenine reduced viral replication. CONCLUSION: This study revealed that the virus (H1N1) titre was controlled in a time-dependent manner following autophagy induction in host cells. Manipulation of autophagy during the IV life cycle can be targeted both for antiviral aims and for increasing viral yield for virus production.
PURPOSE: Autophagy plays a key role in host defence responses against microbial infections by promoting degradation of pathogens and participating in acquired immunity. The interaction between autophagy and viruses is complex, and this pathway is hijacked by several viruses. Influenza virus (IV) interferes with autophagy through its replication and increases the accumulation of autophagosomes by blocking lysosome fusion. Thus, autophagy could be an effective area for antiviral research. METHODOLOGY: In this study, we evaluated the effect of autophagy on IV replication. Two cell lines were transfected with Beclin-1 expression plasmid before (prophylactic approach) and after (therapeutic approach) IV inoculation.Results/Key findings. Beclin-1 overexpression in the cells infected by virus induced autophagy to 26 %. The log10haemagglutinin titre and TCID50 (tissue culture infective dose giving 50 % infection) of replicating virus were measured at 24 and 48 h post-infection. In the prophylactic approach, the virus titre was enhanced significantly at 24 h post-infection (P≤0.01), but it was not significantly different from the control at 48 h post-infection. In contrast, the therapeutic approach of autophagy induction inhibited the virus replication at 24 and 48 h post-infection. Additionally, we showed that inhibition of autophagy using 3-methyladenine reduced viral replication. CONCLUSION: This study revealed that the virus (H1N1) titre was controlled in a time-dependent manner following autophagy induction in host cells. Manipulation of autophagy during the IV life cycle can be targeted both for antiviral aims and for increasing viral yield for virus production.
Authors: Jianzhou Cui; Dhakshayini Morgan; Dao Han Cheng; Sok Lin Foo; Gracemary L R Yap; Patrick B Ampomah; Suruchi Arora; Karishma Sachaphibulkij; Balamurugan Periaswamy; Anna-Marie Fairhurst; Paola Florez De Sessions; Lina H K Lim Journal: Cells Date: 2020-06-04 Impact factor: 6.600