Talk abstracts
Talk on Saturday 12:15-12:35pm submitted by Anna M. Kietrys
Circular RNAs: an underdog of HIV diagnostics
Jian Shi (Chemistry Department, Carnegie Mellon University), Megan L. Van Horn (Chemistry Department, Carnegie Mellon University), Marta Rachwalak (Chemistry Department, Carnegie Mellon University), Anna M. Kietrys (Chemistry Department, Carnegie Mellon University)
Abstract:
The Human Immunodeficiency Virus (HIV) targets the human immune system and compromises defense against many other infections. At the end of 2021, it affected 38.4 million people around the globe: with a high mortality rate of 4.7% [1, 2]. Early and efficient diagnostics are crucial to minimize the spread of HIV worldwide. Currently available lab tests give reliable results after 2 weeks post infection, and self-tests after 4 weeks [3]. However, the first few days post exposition are crucial, as the faster antiviral therapies are introduced, the faster virus proliferation stops and the overall patient outcome improves. Therefore, there is a strong need for a new biomarker to screen early HIV infection (EHI) in patients in the first few days post exposition.
Our group addressed this problem by looking closer at circular RNAs (circRNAs) expression profiles. These understudied molecules are involved in the pathogenesis of EHI, a critical period that determines disease severity and progression to AIDS [4]. We focused on HIV type 1 (HIV-1), the more prevalent and pathogenic type worldwide [5]. To identify potential circRNAs correlated with EHI, we used bioinformatic methods to conduct differential expression analysis on multiple existing human RNAseq data collected from CD4+ T cells at different times post-infection from 18 EHI and 17 healthy controls. To compare the role of circRNA in EHI and latent HIV infection, we also performed a differential analysis of circRNA on 51 latent HIV samples and 4 healthy controls collected from whole blood.
We identified a total of 56 DE circRNAs related to EHI, 49 of which are downregulated. The median length of the 56 DE circRNAs is 456nt, close to the average length of circRNA, which is 500nt. There are 7 DE circRNAs shown up in more than two sampling windows post-infection. We believe these circRNAs are important in EHI. Through GO analysis, we found these circRNAs may affect HIV-1 infectivity by altering HIV binding, transport, integration, and viral reservoirs. Finally, 3 DE circRNAs are shown to be involved in latent phase HIV infections. However, none of these circRNAs is differentially expressed in EHI, suggesting that some circRNA-regulated events are unique to EHI. We believe that understanding the role of circRNAs in the etiology of EHI may contribute to the development of more effective HIV diagnostic tools and therapeutics.
References:
[1] HIV. https://www.who.int/data/gho/data/themes/hiv-aids (accessed Sep 10, 2022).
[2] HIV-related death rate in U.S. fell by half from 2010 to 2017 press release. https://www.cdc.gov/nchhstp/newsroom/2020/hiv-related-death-rate-press-release.html (accessed Sep 10, 2022).
[3] https://www.cdc.gov/hiv/basics/hiv-testing/hiv-window-period.html
[4] Zhang, Y.; Zhang, H.; An, M.; Zhao, B.; Ding, H.; Zhang, Z.; He, Y.; Shang, H.; Han, X. Crosstalk in Competing Endogenous RNA Networks Reveals New Circular RNAS Involved in the Pathogenesis of Early HIV Infection. Journal of Translational Medicine 2018, 16 (1).
[5] Gilbert, P. B.; McKeague, I. W.; Eisen, G.; Mullins, C.; Guéye-NDiaye, A.; Mboup, S.; Kanki, P. J. Comparison of HIV-1 and HIV-2 Infectivity from a Prospective Cohort Study in Senegal. Statistics in Medicine 2003, 22 (4), 573–593.
Keywords: Circular RNA, HIV, Biomarkers