Molecular Dissection of Herpes Simplex Virus Type 1 to Elucidate Molecular Mechanisms Behind Latency and Comparison of Its Codon Usage Patterns with Genes Modulated During Alzheimer’s Disease as a Part of Host-Pathogen Interaction

Article type: Research Article

Authors: Gurjar, Pankaj^{a; b; *} | Khan, Azmat Ali^{c; *} | Alanazi, Amer M.^c | Vasil’ev, Vasilii G.^d | Zouganelis, George^{e; *} | Alexiou, Athanasios^{b; f}

Affiliations: [a] Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India | [b] Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, Australia | [c] Department of Pharmaceutical Chemistry, Pharmaceutical Biotechnology Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia | [d] RERC Pharmacy, RUDN University, Moscow, Russian Federation | [e] School of Human Sciences, College of Life and Natural Sciences, University of Derby, Derby, UK | [f] AFNP Med, Vienna, Austria

Correspondence: [*] Correspondence to: Pankaj Gurjar, Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia. E-mail: [email protected] and George Zouganelis, School of Human Sciences, College of Life and Natural Sciences, University of Derby, Kedleston Road, Derby, DE22 1GB, UK. [email protected] and Azmat Ali Khan, Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. E-mail: [email protected].

Abstract: Background:Herpes simplex virus type 1 (HSV-1) is associated with Alzheimer’s disease, which goes into a cycle of latency and reactivation. The present study was envisaged to understand the reasons for latency and specific molecular patterns present in the HSV-1. Objective:The objective is the molecular dissection of Herpes simplex virus type 1 to elucidate molecular mechanisms behind latency and compare its codon usage patterns with genes modulated during Alzheimer’s disease as a part of host-pathogen interaction. Methods:In the present study, we tried to investigate the potential reasons for the latency of HSV-1 virus bioinformatically by determining the CpG patterns. Also, we investigated the codon usage pattern, the presence of rare codons, codon context, and protein properties. Results:The top 222 codon pairs graded based on their frequency in the HSV-1 genome revealed that with only one exception (CUG-UUU), all other codon pairs have codons ending with G/C. Considering it an extension of host-pathogen interaction, we compared HSV-1 codon usage with that of codon usage of genes modulated during Alzheimer’s disease, and we found that CGT and TTT are only two codons that exhibited similar codon usage patterns and other codons showed statistically highly significant different codon preferences. Dinucleotide CpG tends to mutate to TpG, suggesting the presence of mutational forces and the imperative role of CpG methylation in HSV-1 latency. Conclusions:Upon comparison of codon usage between HSV-1 and Alzheimer’s disease genes, no similarities in codon usage were found as a part of host-pathogen interaction. CpG methylation plays an imperative role in latency HSV-1.

Keywords: Alzheimer’s disease, codon context, codon usage, Herpes simplex virus type 1, rare codon, virus latency

DOI: 10.3233/JAD-231083

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1111-1123, 2024