ARF4-mediated intracellular transport as a broad-spectrum antiviral target
- simonc2i
- Mar 28
- 1 min read
The Centre for Immunology & Infection and the HKU-Pasteur Research Pole share a new study in Nature Microbiology that explores the role of host factors in viral infection and their potential as antiviral drug targets.
Focusing on ADP-ribosylation factors (ARFs), specifically ARF4, which are crucial in regulating vesicular trafficking within cells, the study reveals that genetic depletion of ARF4 significantly suppresses the infection of various pathogenic RNA viruses, including Zika virus, influenza A virus, and SARS-CoV-2.
Importantly, the findings demonstrate that targeting ARF4 can effectively inhibit viral replication and release, offering promising therapeutic avenues for the development of broad-spectrum antiviral strategies. This research underscores the vital role of ARF4 in viral pathogenesis and its potential as a target for innovative antiviral therapies.
Abstract:
Host factors that are involved in modulating cellular vesicular trafficking of virus progeny could be potential antiviral drug targets. ADP-ribosylation factors (ARFs) are GTPases that regulate intracellular vesicular transport upon GTP binding. Here we demonstrate that genetic depletion of ARF4 suppresses viral infection by multiple pathogenic RNA viruses including Zika virus (ZIKV), influenza A virus (IAV) and SARS-CoV-2. Viral infection leads to ARF4 activation and virus production is rescued upon complementation with active ARF4, but not with inactive mutants. Mechanistically, ARF4 deletion disrupts translocation of virus progeny into the Golgi complex and redirects them for lysosomal degradation, thereby blocking virus release. More importantly, peptides targeting ARF4 show therapeutic efficacy against ZIKV and IAV challenge in mice by inhibiting ARF4 activation. Our findings highlight the role of ARF4 during viral infection and its potential as a broad-spectrum antiviral target for further development.
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