Personal historical perspective of HIV: part 11.

All animal life on earth is thought to have a common origin and have common genetic mechanisms. Evolution has enabled differentiation of species. Pathogens likewise have evolved within various species and mostly come to a settled dynamic equilibrium such that co-existence results (pathogens ideally should not kill their hosts). Problems arise when pathogens jump species because the new host had not developed any resistance. These infections from related species are known as zoonoses. COVID-19 is the latest example of a virus entering another species but HIV (and various strains of influenza) were previous examples. HIV entered the human population from monkeys in Africa. These two papers outline the underlying principle of HIV and the differing epidemiologies in Africa, the USA and in Edinburgh. The underlying immunosuppression of HIV in Africa was initially hidden behind common infections and HIV first came to world awareness in focal areas of the USA as a disease seemingly limited to gay males. The epidemic of intravenous drug abuse in Edinburgh was associated with overlapping epidemics of bloodborne viruses like hepatitis B, hepatitis C and HIV.

Long non-coding RNAs in virus-related cancers.

Some viral infections lead to tumourigenesis explained by a variety of underlying molecular mechanisms. Long non-coding RNAs (lncRNAs) have the potential to be added to this list due to their diverse mechanisms in biological functions and disease processes via gene alternation, transcriptional regulation, protein modification, microRNA sponging and interaction with RNA/DNA/proteins. In this review, we summarise the dysregulation and mechanism of lncRNAs in virus-related cancers focussing on Hepatitis B virus, Epstein-Barr virus, Human Papillomavirus. We will also discuss the potential implications of lncRNAs in COVID-19.

Adenoviral Vectors: Potential as Anti-HBV Vaccines and Therapeutics.

Adenoviral vaccines have been at the front line in the fight against pandemics caused by viral infections such as Ebola and the coronavirus disease 2019. This has revived an interest in developing these vectors as vaccines and therapies against other viruses of health importance such as hepatitis B virus (HBV). Current hepatitis B therapies are not curative; hence, chronic hepatitis B remains the major risk factor for development of liver disease and death in HBV-infected individuals. The ability to induce a robust immune response and high liver transduction efficiency makes adenoviral vectors attractive tools for anti-HBV vaccine and therapy development, respectively. This review describes recent developments in designing adenoviral-vector-based therapeutics and vaccines against HBV infection.

Treating Hepatitis B Virus in Times of COVID-19: The Case for Clinical Pharmacogenomics Research in Tenofovir-Induced Kidney Toxicity.

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.

Hepatitis B virus (HBV) codon adapts well to the gene expression profile of liver cancer: an evolutionary explanation for HBV's oncogenic role.

Due to the evolutionary arms race between hosts and viruses, viruses must adapt to host translation systems to rapidly synthesize viral proteins. Highly expressed genes in hosts have a codon bias related to tRNA abundance, the primary RNA translation rate determinant. We calculated the relative synonymous codon usage (RSCU) of three hepatitis viruses (HAV, HBV, and HCV), SARS-CoV-2, 30 human tissues, and hepatocellular carcinoma (HCC). After comparing RSCU between viruses and human tissues, we calculated the codon adaptation index (CAI) of viral and human genes. HBV and HCV showed the highest correlations with HCC and the normal liver, while SARS-CoV-2 had the strongest association with lungs. In addition, based on HCC RSCU, the CAI of HBV and HCV genes was the highest. HBV and HCV preferentially adapt to the tRNA pool in HCC, facilitating viral RNA translation. After an initial trigger, rapid HBV/HCV translation and replication may change normal liver cells into HCC cells. Our findings reveal a novel perspective on virus-mediated oncogenesis.

Alignment-free sequence comparison for virus genomes based on location correlation coefficient.

Coronaviruses (especially SARS-CoV-2) are characterized by rapid mutation and wide spread. As these characteristics easily lead to global pandemics, studying the evolutionary relationship between viruses is essential for clinical diagnosis. DNA sequencing has played an important role in evolutionary analysis. Recent alignment-free methods can overcome the problems of traditional alignment-based methods, which consume both time and space. This paper proposes a novel alignment-free method called the correlation coefficient feature vector (CCFV), which defines a correlation measure of the L-step delay of a nucleotide location from its location in the original DNA sequence. The numerical feature is a 16×L-dimensional numerical vector describing the distribution characteristics of the nucleotide positions in a DNA sequence. The proposed L-step delay correlation measure is interestingly related to some types of L+1 spaced mers. Unlike traditional gene comparison, our method avoids the computational complexity of multiple sequence alignment, and hence improves the speed of sequence comparison. Our method is applied to evolutionary analysis of the common human viruses including SARS-CoV-2, Dengue virus, Hepatitis B virus, and human rhinovirus and achieves the same or even better results than alignment-based methods. Especially for SARS-CoV-2, our method also confirms that bats are potential intermediate hosts of SARS-CoV-2.