TY - JOUR
T1 - Variations in the abortive hiv-1 rna hairpin do not impede viral sensing and innate immune responses
AU - Stunnenberg, Melissa
AU - van Hamme, John L.
AU - Das, Atze T.
AU - Berkhout, Ben
AU - Geijtenbeek, Teunis B. H.
N1 - Funding Information: Funding: This research was funded by Aidsfonds (P-9906) and the European Research Council (Advanced grant 670424). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation in the TAR RNA structure renders the virus replication-incompetent, effects on viral sensing remain unclear. Here, we investigated the role of TAR RNA structure and stability on viral sensing. TAR mutants with deletions in the TAR hairpin that enhanced thermodynamic stability increased antiviral responses. Strikingly, TAR mutants with lower stability due to destabilization of the TAR hairpin also increased antiviral responses without affecting pro-inflammatory responses. Moreover, mutations that affected the TAR RNA sequence also enhanced specific antiviral responses. Our data suggest that mutations in TAR of replication-incompetent viruses can still induce immune responses via viral sensors, hereby underscoring the robustness of HIV-1 RNA sensing mechanisms.
AB - The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation in the TAR RNA structure renders the virus replication-incompetent, effects on viral sensing remain unclear. Here, we investigated the role of TAR RNA structure and stability on viral sensing. TAR mutants with deletions in the TAR hairpin that enhanced thermodynamic stability increased antiviral responses. Strikingly, TAR mutants with lower stability due to destabilization of the TAR hairpin also increased antiviral responses without affecting pro-inflammatory responses. Moreover, mutations that affected the TAR RNA sequence also enhanced specific antiviral responses. Our data suggest that mutations in TAR of replication-incompetent viruses can still induce immune responses via viral sensors, hereby underscoring the robustness of HIV-1 RNA sensing mechanisms.
KW - Abortive HIV-1 RNA
KW - Antiviral immunity
KW - Human immunodeficiency virus 1
KW - Pattern recognition receptors
KW - Sequence variation
KW - TAR RNA structure
KW - TAR hairpin
KW - Thermodynamic stability
KW - Viral sensing
UR - http://www.scopus.com/inward/record.url?scp=85111089760&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/pathogens10070897
DO - https://doi.org/10.3390/pathogens10070897
M3 - Article
C2 - 34358047
SN - 2076-0817
VL - 10
JO - Pathogens (Basel, Switzerland)
JF - Pathogens (Basel, Switzerland)
IS - 7
M1 - 897
ER -