Authors
Rout, S. S., Stewart, M. T. E., Seidel, N. B., Dittmer, U., Sutter, K., Lavender, K. J.
Abstract
Type I IFN, including IFN-, induces the expression of antiviral restriction factors that can interfere with multiple steps of the HIV-1 replication cycle. Humans have 13 IFN- genes which encode 12 different IFN- subtypes. Our previous work in HIV-1 infected humanized mice showed that IFN-14 treatment more potently controlled HIV-1 than treatment with the clinically approved IFN-2 subtype. However, the mechanisms behind the more potent control of HIV-1 by IFN-14 are unknown. The IFN-14 subtype is known to more potently induce the expression of the restriction factors MX2 and ISG15 and increased APOBEC3G signature mutations in vivo compared to IFN-2. To study the importance of each of these restriction factors in mediating the potent control of HIV-1, we used a CRISPR-Cas9 lentivirus system to create stable knockouts in the MT4C5 cell line that is susceptible to HIV-1 but does not produce measurable amounts of endogenous IFN-. Knock out of ISG15, but not MX2, eliminated differences in viral suppression after IFN-14 and IFN-2 treatment. Similarly, APOBEC3G deletion eliminated differences in viral suppression and the number of infectious particles produced after IFN-14 and IFN-2 treatment. Furthermore, APOBEC3G deletion resulted in significantly fewer GG[->]AG mutations in viral DNA isolated from target cells incubated with supernatant from IFN-14 treated groups. However, APOBEC3G knock out did not result in significant increases in vDNA compared to the wild type in any experimental group. Overall, elimination of APOBEC3G and ISG15 impaired IFN-14-mediated suppression of HIV-1, highlighting them as downstream effectors of IFN-14's more potent anti-HIV-1 activity.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 04 Nov 2025.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 36
- Comments 0