1. Human Codon Usage: The Genetic Basis of Pathogen Latency
- Author
-
Darja Kanduc
- Subjects
0301 basic medicine ,pathogen latency ,protein synthesis ,cross-reactivity ,Biology ,QH426-470 ,codon optimization ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Protein biosynthesis ,Genetics ,Latency (engineering) ,Gene ,Pathogen ,RC254-282 ,Innate immune system ,codon usage ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Codon usage bias ,Identification (biology) ,Original Article ,DNA ,(re)activation ,trnas - Abstract
Infectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present study (1) analyzed the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) described how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) framed human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it was shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics.
- Published
- 2021