Effects of Arbovirus Multi-Host Life Cycles on Dinucleotide and Codon Usage Patterns

Abstract

Arthropod-borne viruses (arboviruses) of vertebrates including dengue, zika, chikungunya, Rift Valley fever, and blue tongue viruses cause extensive morbidity and mortality in humans, agricultural animals, and wildlife across the globe. As obligate intercellular pathogens, arboviruses must be well adapted to the cellular and molecular environment of both their arthropod (invertebrate) and vertebrate hosts, which are vastly different due to hundreds of millions of years of separate evolution. Here we discuss the comparative pressures on arbovirus RNA genomes as a result of a dual host life cycle, focusing on pressures that do not alter amino acids. We summarize what is currently known about arboviral genetic composition, such as dinucleotide and codon usage, and how cyclical infection of vertebrate and invertebrate hosts results in different genetic profiles compared with single-host viruses. To serve as a comparison, we compile what is known about arthropod tRNA, dinucleotide, and codon usages and compare this with vertebrates. Additionally, we discuss the potential roles of genetic robustness in arboviral evolution and how it may vary from other viruses. Overall, both arthropod and vertebrate hosts influence the resulting genetic composition of arboviruses, but a great deal remains to be investigated.

Codon Usage in the Iflaviridae Family Is Not Diverse Though the Family Members Are Isolated from Diverse Host Taxa

“…However, we found that the nucleotide composition and codon usage in the Iflaviridae family does not vary in accordance with viral host taxa. This result is consistent with the findings that an animal host has a relatively smaller impact on the viral dinucleotide composition [47]; moreover, a host association drives the viral codon usage, but a host does not serve as a template for the viral codon usage [48]. Virus host shift events and host range affect viral codon usage patterns in that narrow-host-range viruses match hosts' tRNA pools better than broad-host-range viruses [19].…”

CpG-Recoding in Zika Virus Genome Causes Host-Age-Dependent Attenuation of Infection With Protection Against Lethal Heterologous Challenge in Mice

“…Only CpG-recoded influenza virus has been extensively studied in adult mouse models (4). Codon pair deoptimized viruses were studied in animal models as well (58,59); however, effects of codon pair bias deoptimization may arise through the unintended increase in CpG and UpA dinucleotide frequencies FIGURE 10 | Protective efficacy of WT and CpG-recoded ZIKV variants in adult mice. ZIKV-specific (A) and neutralizing (B) Abs at 28 days after immunization with 10 5 TCID 50 of WT or CpG-recoded ZIKV variants.…”

Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains

“…In serial mouse passage, we observed similar suppression of UpA dinucleotides, but saw even more stringent suppression of CpG dinucleotides. The observed ZIKV dinucleotide usage patterns in mice and mosquitoes align with the dinucleotide usage biases in each host (Lobo et al, 2009; Sexton and Ebel, 2019). Mosquitoes and vertebrates exhibit disparate dinucleotide usage biases in their transcriptomes, and arbovirus genomes typically adopt an intermediate usage pattern at consensus-level compared to single-host viruses, presumably to accommodate both vector and vertebrate host environments (Halbach et al, 2017; Sexton and Ebel, 2019).…”

“…The observed ZIKV dinucleotide usage patterns in mice and mosquitoes align with the dinucleotide usage biases in each host (Lobo et al, 2009; Sexton and Ebel, 2019). Mosquitoes and vertebrates exhibit disparate dinucleotide usage biases in their transcriptomes, and arbovirus genomes typically adopt an intermediate usage pattern at consensus-level compared to single-host viruses, presumably to accommodate both vector and vertebrate host environments (Halbach et al, 2017; Sexton and Ebel, 2019). To our knowledge, this is the first evidence of the dinucleotide selective pressure acting on a multi-host virus at the sub-consensus level, as opposed to the consensus level.…”

“…Lastly, adaptation to host dinucleotide usage biases was compared between passage types by tracking changes in CpG and UpA dinucleotide usage within virus populations. In mice and humans, CpG and UpA dinucleotides are suppressed within the host genome (Sexton and Ebel, 2019), whereas only UpA dinucleotides are suppressed within mosquito genomes. In line with host and vector biases, CpG usage was strongly suppressed after the first serial passage in mice (linear regression non-zero slope F test, P =0.0060), but no suppression was observed during serial mosquito or alternating passage (linear regression slope>0; Figure 6C).…”