Possible Effect of Hyperthermia on Accessibility of Cellular and Viral miRNAs to mRNAs Involved in HIV Replication.

MORANDO, NICOLÁS; GUZMAN, LUCÍA FLORENCIA; PANDO, MARÍA DE LOS ÁNGELES; RABINOVICH, DANIEL

Madrid

Congreso; HIV Research for Prevention 2018: AIDS Vaccine, Microbicide and ARV-based Prevention Science (HIVR4P); 2018

BackgroundCocaine can affect the expression of various miRNAs involved in HIV replication; it can also induce hyperthermia up to 43°C. This suggests a possible indirect effect of cocaine on miRNA-mediated HIV regulation, since changes in temperature can affect mRNA secondary structure altering the accessibility of miRNA to its binding site. Our goal was to perform an in silico analysis of the effect of temperature on binding sites of miRNAs able to affect HIV replication. MethodsCellular and viral-encoded miRNAs involved in HIV replication, with cellular or viral mRNA targets, were identified from the literature. Sequences of these miRNAs were obtained from the miRBase database and the target sites within the corresponding mRNAs were identified using BiBiserv 2(RNAhybrid). mRNA secondary structures at 37°C and 43°C, with their corresponding free energy(ΔG) values, were predicted using UNAFOLD(mFold2.3). For each temperature, the difference in ΔG (ΔΔG) between the most stable structure (where the bases at the miRNA binding site tend to be paired) and the structure where all of these bases are unpaired was calculated. Results48 miRNA-mRNA pairs were analyzed: 22 cellular miRNA-viral mRNA pairs, 22 cellular miRNA-cellular mRNA pairs, 3 viral miRNA-viral mRNA pairs and 1 viral miRNA-viral mRNA pair. In 46 cases a rise in temperature was predicted to lower the ΔΔG, implying higher accessibility to the target site. When considering only the bases within the seed region, this same effect was observed in 35 pairs. When comparing the 43°C structure with respect to the 37°C structure, changes in the pattern of paired nucleotides at the miRNA binding site were observed in 14 cases: 1 case with no net change, 7 cases with a higher number and 6 cases with a lower number of paired nucleotides. ConclusionIn silico analyses suggest that changes in temperature can alter miRNA access to mRNAs involved in HIV replication. This could be relevant for patients with HIV who use substances that cause hyperthermia.