Phylogenetic and Timescale Analysis of Barmah Forest Virus as Inferred from Genome Sequence Analysis

Abstract

<jats:p>Barmah Forest virus (BFV) is a medically important mosquito-borne alphavirus endemic to Australia. Symptomatic disease can be a major cause of morbidity, associated with fever, rash, and debilitating arthralgia. BFV disease is similar to that caused by Ross River virus (RRV), the other major Australian alphavirus. Currently, just four BFV whole-genome sequences are available with no genome-scale phylogeny in existence to robustly characterise genetic diversity. Thirty novel genome sequences were derived for this study, for a final 34-taxon dataset sampled over a 44 year period. Three distinct BFV genotypes were characterised (G1–3) that have circulated in Australia and Papua New Guinea (PNG). Evidence of spatio-temporal co-circulation of G2 and G3 within regions of Australia was noted, including in the South West region of Western Australia (WA) during the first reported disease outbreaks in the state’s history. Compared with RRV, the BFV population appeared more stable with less frequent emergence of novel lineages. Preliminary in vitro assessment of RRV and BFV replication kinetics found that RRV replicates at a significantly faster rate and to a higher, more persistent titre compared with BFV, perhaps indicating mosquitoes may be infectious with RRV for longer than with BFV. This investigation resolved a greater diversity of BFV, and a greater understanding of the evolutionary dynamics and history was attained.</jats:p>

The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence

“…Notably, Aaskov et al (2011) also suggested that TVS motifs within HADTVSLD-STVS/L duplicate regions are repeated four times in a less conserved form (black boxes) (Figure 6), and they might be marks from previous duplication events in RRV nsP3 HVD. In addition, from our observations, these suggested insertion or duplications motifs from Michie et al (2020) and Aaskov et al (2011) overlap with each other at the HADTVSLD residues at position 344-351. Interestingly, they also observed 5 aa deletions within the 12 aa insertion/duplication at position 342-346, which occurred in DC36025 (accession no: MN038209), a mosquito isolate.…”

“…However, only SFV has the extended version of the P-rich region as mentioned, while SINV and CHIKV have a shorter initial motif, P(I/V)(P/A)PPR [3]. The number of P-rich regions of the nsP3 HVD and their positions can vary according to the alphavirus species, for example, there is one region in MAYV, SFV, CHIKV, ONNV, and SINV; two regions in NW alphaviruses VEEV, EEEV, and WEEV; and four regions in RRV and BFV-all found at different positions within nsP3 HVD [2,37,79,136,186].…”

Genome Sequence Analysis of First Ross River Virus Isolate from Papua New Guinea Indicates Long-Term, Local Evolution

“…Barmah Forest virus is an alphavirus that was thought to be exclusively endemic to Australia, until its recent isolation from a febrile patient in PNG with no history of international travel [ 30 ]. Temporal analysis dates the emergence of the unique BFV PNG clade to 50–120 years ago, likely facilitated by movement of large numbers of Australian troops into the Asia Pacific region during World War 2 [ 31 ]. Consistent with our findings for RRV, it appears that exchange of BFV between Australia and PNG is sporadic, despite the theoretical potential for more regular spread via mobile vertebrate hosts such as migratory birds [ 30 , 31 ].…”

Persistent Joint Pain Following Arthropod Virus Infections

“…BFV is an alphavirus that is most commonly found in Australia. BFV was initially isolated in 1974 from Culex annulirostris mosquitos that were collected in the Barmah Forest in Victoria, Australia [ 47 ]. The first human cases were reported in Australia in 1986 [ 48 ].…”

“…In the past 10 years, about 1600 annual cases of BFV have been reported in Australia [ 50 ]. There have been several larger outbreaks reported in Australia in 1992, 1993, 1994, 1995, and 2002 [ 47 ]. BFV may have an avian or bat host and is transmitted by mosquitoes to humans [ 48 ].…”