PurUUpurU: An Oligonucleotide Virulence Factor in RNA Viruses

Abstract

BackgroundThe copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with the severity of acute illness. This study aimed to determine whether purUUpurU content correlates with virulence in other single-strand RNA (ssRNA) viruses that vary in clinical severity. MethodologyWe determined the copy number of purUUpurU in the genomes of two subtypes of human respiratory syncytial virus (RSV), respiratory syncytial virus A (RSV-A), and respiratory syncytial virus B (RSV-B), which vary in clinical severity. In addition, we determined the purUUpurU content of the four ebolaviruses that cause human disease, dengue virus, rabies virus, human rhinovirus-A, poliovirus type 1, astrovirus, rubella, yellow fever virus, and measles virus. Viral nucleotide sequence files were downloaded from the National Center for Biotechnology Information (NCBI)/National Institutes of Health website. In addition, we determined the cumulative case fatality rate of 20 epidemics of the Ebola virus and compared it with that of the other human ebolaviruses. ResultsThe genomic purUUpurU content correlated with the severity of acute illness caused by both subtypes of RSV and human ebolaviruses. The lowest purUUpurU content was in the genome of the rubella virus, which causes mild disease. ConclusionsThe quantity of genomic purUUpurU is a virulence factor in ssRNA viruses. Blood hyperviscosity is one mechanism by which purUUpurU causes pathology. Comparative quantitative genomic analysis for purUUpurU will be helpful in estimating the risk posed by emergent ssRNA viruses.

COVID-19 Demonstrates That Inflammation Is a Hyperviscous State

“…We have putatively identified the oligonucleotide purUUpurU as a virulence factor in single-strand RNA (ssRNA) viruses including SARS-CoV-2 [ 30 ]. In vitro data of TLR8-bearing myeloid cells incubated with oligonucleotide precursors to purUUpurU demonstrates upregulation of pro-inflammatory cytokines [ 3 ].…”

“…In general, by driving cytokine expression, the copy number of purUUpurU in their genome correlates with the severity of acute illness caused by ssRNA viruses. PurUUpurU is one driver of the symptoms seen in nonspecific viral syndromes and the prodromal phase of many specific viral diseases [ 30 ].…”

“…It has also provided insight into the cause of the marked elevations of cytokines seen in coronaviral and ebolavirus infections. These elevations may be driven as much, or even more, by the viral genome as by loss of control of the host immune response [ 30 ].…”