Poster abstracts
Poster number 135 submitted by Jian Shi
Identification of Circular RNAs in Early Human Immunodeficiency Virus Infection
Jian Shi (Department of Chemistry at Carnegie Mellon University), Megan L. Van Horn (Department of Chemistry at Carnegie Mellon University), Marta Rachwalak (Department of Chemistry at Carnegie Mellon University), Anna M. Kietrys (Department of Chemistry at Carnegie Mellon University)
Abstract:
The Human Immunodeficiency Virus (HIV) targets the human immune system and compromises defense against many other infections. It affected 38.4 million people worldwide at the end of 2021 and had a high mortality rate of 4.7% [1, 2]. Circular RNA (circRNA) is an understudied molecule involved in the pathogenesis of early HIV infection (EHI), a critical period that determines disease severity and progression to AIDS [3]. Understanding the role of circRNAs in the etiology of EHI may contribute to the development of more effective HIV therapeutics.
Our group focused on HIV type 1 (HIV-1), the more prevalent and pathogenic type worldwide [4]. To identify potential circRNAs correlated with EHI, our group used bioinformatic methods to conduct differential expression analysis on multiple existing human RNA-Seq data collected from CD4+ T cells at different times post-infection from 18 EHI and 17 healthy controls. Characteristics and gene ontology (GO) of the differentially expressed (DE) circRNAs are analyzed. 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.
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] 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).
[4] 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