Impaired influenza A virus replication by the host restriction factor SAMHD1 which inhibited by PA-mediated dephosphorylation of the host transcription factor IRF3.

BACKGROUND: Influenza A virus (IAV) can cause severe and life-threatening illness in humans and animals. Therefore, it is important to search for host antiviral proteins and elucidate their antiviral mechanisms for the development of potential treatments. As a part of human innate immunity, host restriction factors can inhibit the replication of viruses, among which SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) can restrict the replication of viruses, such as HIV and enterovirus EV71. Viruses also developed countermeasures in the arms race with their hosts. There are few reports about whether SAMHD1 has a restriction effect on IAV. METHODS: To investigate the impact of IAV infection on SAMHD1 expression in A549 cells, we infected A549 cells with a varying multiplicity of infection (MOI) of IAV and collected cell samples at different time points for WB and RT-qPCR analysis to detect viral protein and SAMHD1 levels. The virus replication level in the cell culture supernatant was determined using TCID50 assay. Luciferase assay was used to reveal that H5N1 virus polymerase acidic protein (PA) affected the activity of the SAMHD1 promoter. To assess the antiviral capacity of SAMHD1, we generated a knockdown and overexpressed cell line for detecting H5N1 replication. RESULTS: In this study, we observed that SAMHD1 can restrict the intracellular replication of H5N1 and that the H5N1 viral protein PA can downregulate the expression of SAMHD1 by affecting SAMHD1 transcriptional promoter activity. We also found that SAMHD1's ability to restrict H5N1 is related to phosphorylation at 592-tyrosine. CONCLUSIONS: In conclusion, we found that SAMHD1 may affect the replication of IAVs as a host restriction factor and be countered by PA. Furthermore, SAMHD1 may be a potential target for developing antiviral drugs.

NEWSPAPER-REPORTING ON SUICIDES DURING THE COVID-19 LOCKDOWN IN PAKISTAN: A CONTENT ANALYSIS.

BACKGROUND: Suicide is a social relevant issue and a leading cause of deaths in the world; it has been reported that COVID-19 has significantly increased the rate of suicide worldwide. This study aimed to review media reporting on suicide cases occurred in Pakistan during the COVID-19 lockdown. SUBJECTS AND METHODS: A content analysis has been performed considering the electronic version of the daily Kawish newspaper reporting suicide cases from March to August 2020 in Pakistan. RESULTS: A total of 213 news regarding suicide in Pakistan during the lockdown period were identified. Suicide committers reported age ranging 19-30 years old, and the majority of them were males (74%). Suicide methods ranged as following: harmful practices (79%) > hanging (37%) > self-poisoning (28%). Factors associated to the risk of suicide were: familial discords (36%), poverty (21%) and joblessness (14%). CONCLUSION: Findings of this study have shown that pandemic lockdown in Pakistan have increased the number of factors, such as family issues, unemployment and poverty, leading to suicide especially in young males. The report of suicides may have an impact on the public general opinion and a responsible news-reporting is needed by press agencies and media.