Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts

Abstract

Virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. Flaviviridae family is composed of fast evolving RNA viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. These host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. Flaviviridae viruses which infect a single host lineage would be subjected to specific host-induced pressures and, therefore, selected by them. In this work we compare the genomic evolutionary patterns of Flaviviridae viruses and their hosts in an attempt to uncover coevolutionary processes inducing common features in such disparate groups. Especially, we have analyzed dinucleotide and codon usage patterns in the coding regions of vertebrate and invertebrate organisms as well as in Flaviviridae viruses which specifically infect one or both host types. The two host groups possess very distinctive dinucleotide and codon usage patterns. A pronounced CpG under-representation was found in the vertebrate group, possibly induced by the methylation-deamination process, as well as a prominent TpA decrease. The invertebrate group displayed only a TpA frequency reduction bias. Flaviviridae viruses mimicked host nucleotide motif usage in a host-specific manner. Vertebrate-infecting viruses possessed under-representation of CpG and TpA, and insect-only viruses displayed only a TpA under-representation bias. Single-host Flaviviridae members which persistently infect mammals or insect hosts (Hepacivirus and insect-only Flavivirus, respectively) were found to posses a codon usage profile more similar to that of their hosts than to related Flaviviridae. We demonstrated that vertebrates and mosquitoes genomes are under very distinct lineage-specific constraints, and Flaviviridae viruses which specifically infect these lineages appear to be subject to the same evolutionary pressures that shaped their host coding regions, evidencing the lineage-specific coevolutionary processes between the viral and host groups.

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

“…This pattern is most visible in the overlapping distribution of virus clades and various Hyalomma species, consistent with a lengthy history of co-evolution of the virus with its tick vectors. A similar pattern has been observed for tick-borne flaviviruses (Lobo et al, 2009). The relative regional homogeneity of CCHFV has been demonstrated in Turkey by a systematic sampling of local isolates, which showed little genetic diversity and no evidence of ''invasion'' by strains from other regions, suggesting that the marked increase in CCHF that has occurred in Turkey over the past decade has been caused by viruses indigenous to the country (Kalaycioglu et al, 2012).…”

Culex Flavivirus and West Nile Virus Mosquito Coinfection and Positive Ecological Association in Chicago, United States

“…Such positive association could result from immunological processes within individual mosquitoes. For example, a recent study has shown that insect-specific Flavivirus genomes are subject to similar selective pressures as those operating on the genomes of their mosquito hosts, suggesting host-virus coevolution (Lobo et al 2009). If so, then CxFV may have evolved mechanisms to reduce immune recognition by its mosquito host, which could facilitate secondary infections with similar agents such as WNV.…”

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

“…Krishnan et al (2008) used a human-genome-wide RNAi screen to identify 305 host proteins potentially involved in WNV infection and found a complex dependence of WNV on the host cell physiology, which required a wide variety of molecules and cellular pathways for successful infection. In addition to analyzing pathways of virus infection in hosts, examining the overall codon usage for an RNA virus open reading frame (ORF) is useful for estimating the evolutionary processes and genetic features of viruses that respond or adapt to the host cell environment (Bahir et al, 2009;Lobo et al, 2009;Wong et al, 2010;Zhou et al, 2013a,b). Recent progress has been made in measuring viral protein translation at the level of synonymous codon usage bias (Sanchez et al, 2003;Burns et al, 2006;Mueller et al, 2006;Bahir et al, 2009;Wong et al, 2010;Poyry and Jackson, 2011;Zhou et al, 2011); however, the contribution of the WNV coding sequence to replication efficiency remains unclear.…”