TY - JOUR
T1 - The landscape of ifn/isg signaling in hiv-1-infected macrophages and its possible role in the hiv-1 latency
AU - Rojas, Masyelly
AU - Luz-Crawford, Patricia
AU - Soto-Rifo, Ricardo
AU - Reyes-Cerpa, Sebastián
AU - Toro-Ascuy, Daniela
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9/9
Y1 - 2021/9/9
N2 - A key characteristic of Human immunodeficiency virus type 1 (HIV-1) infection is the generation of latent viral reservoirs, which have been associated with chronic immune activation and sustained inflammation. Macrophages play a protagonist role in this context since they are persistently infected while being a major effector of the innate immune response through the generation of type-I interferons (type I IFN) and IFN-stimulated genes (ISGs). The balance in the IFN signaling and the ISG induction is critical to promote a successful HIV-1 infection. Classically, the IFNs response is fine-tuned by opposing promotive and suppressive signals. In this context, it was described that HIV-1-infected macrophages can also synthesize some antiviral effector ISGs and, positive and negative regulators of the IFN/ISG signaling. Recently, epitranscriptomic regulatory mechanisms were described, being the N6-methylation (m6A) modification on mRNAs one of the most relevant. The epitranscriptomic regulation can affect not only IFN/ISG signaling, but also type I IFN expression, and viral fitness through modifications to HIV-1 RNA. Thus, the establishment of replication-competent latent HIV-1 infected macrophages may be due to non-classical mechanisms of type I IFN that modulate the activation of the IFN/ISG signaling network.
AB - A key characteristic of Human immunodeficiency virus type 1 (HIV-1) infection is the generation of latent viral reservoirs, which have been associated with chronic immune activation and sustained inflammation. Macrophages play a protagonist role in this context since they are persistently infected while being a major effector of the innate immune response through the generation of type-I interferons (type I IFN) and IFN-stimulated genes (ISGs). The balance in the IFN signaling and the ISG induction is critical to promote a successful HIV-1 infection. Classically, the IFNs response is fine-tuned by opposing promotive and suppressive signals. In this context, it was described that HIV-1-infected macrophages can also synthesize some antiviral effector ISGs and, positive and negative regulators of the IFN/ISG signaling. Recently, epitranscriptomic regulatory mechanisms were described, being the N6-methylation (m6A) modification on mRNAs one of the most relevant. The epitranscriptomic regulation can affect not only IFN/ISG signaling, but also type I IFN expression, and viral fitness through modifications to HIV-1 RNA. Thus, the establishment of replication-competent latent HIV-1 infected macrophages may be due to non-classical mechanisms of type I IFN that modulate the activation of the IFN/ISG signaling network.
KW - Epitranscriptomic
KW - IFN/ISG response
KW - Latent HIV-1 reservoir
KW - Macrophages
KW - Regulation HIV
KW - Epitranscriptomic
KW - IFN/ISG response
KW - Latent HIV-1 reservoir
KW - Macrophages
KW - Regulation HIV
UR - http://www.scopus.com/inward/record.url?scp=85115890618&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/2a12159d-7494-3840-a5ab-356059ffdbae/
U2 - 10.3390/cells10092378
DO - 10.3390/cells10092378
M3 - Article
C2 - 34572027
AN - SCOPUS:85115890618
SN - 2073-4409
VL - 10
SP - 2378
JO - Cells
JF - Cells
IS - 9
M1 - 2378
ER -