The full-length ORF1 and ORF2 coding sequences were extracted from selected SaV genomes and concatenated for codon usage analysis (see Table 4 for the list of included genome sequences). Codon usage and summary statistic of codon usage bias (N c and N c 9) were calculated using the INCA package version 2.1 [59] , where N c is the effective number of codons in the coding regions of the genome [60] , and N c 9 is the effective number of codons adjusted for background nucleotide composition [61] . For CpG dinucleotide bias analysis, odds ratio of CpG and GpC dinucleotides and the CpG/GpC ratio were calculated as described in previous studies [40, 41] . Odds ratio of #0.78 indicates significant suppression of the dinucleotide, same as the interpretation criteria of previous studies. Symmetrized nucleotide frequencies and dinucleotide odds ratio were not considered in the present study, as SaV genomes consist of positive-sense ssRNA only. To investigate the possible effects of cytosine deamination, genomic GC skew, which is the ratio (G-C)/(G+C), was calculated for the SaV genomes. The strength of the GC skew had been suggested to correlate with the degree of cytosine deamination [41, 44, 62] .  Angiotensin Converting Enzyme (ACE) and ACE2 Bind Integrins and ACE2 Regulates Integrin Signalling The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling. Heart failure is characterised as a decline in cardiac contractility, which is associated with structural changes, collectively termed cardiac remodelling. Cardiac myofibroblasts are key mediators of cardiac remodelling via their proliferation, invasion and secretion of extracellular matrix proteins. Angiotensin II (Ang II) stimulates cardiac myofibroblast transdifferentiation leading to fibrosis. Ang II also stimulates proliferation [1] , NADPH oxidase activation [2] (and thereby reactive oxygen species production), the production of proinflammatory cytokines [3] and the activation of matrix metalloproteinases (MMPs) [4] . As a result, Ang II is a major contributor to the pathology of cardiovascular diseases. Ang II is generated from the biologically inert peptide, Ang I, by the catalytic action of angiotensin converting enzyme (ACE), a key proteolytic step in the renin angiotensin system (RAS). Aberrant functioning of the RAS is a feature of a variety of cardiovascular, renal and other pathologies and ACE inhibitors and Ang II receptor 1 (AT1R) antagonists are widely used in the clinic. Accordingly, ACE inhibition has been shown to prevent cardiac remodelling after myocardial infarction (MI) and preserves cardiac function [5, 6] . A combination of ACE inhibitors and AT1R blockers has been shown to be more effective than either alone [7] . A decade ago a new member of this system was identified, termed angiotensin converting enzyme 2 (ACE2) [8, 9] . ACE2 acts to hydrolyse Ang II into the vasodilator Ang-(1-7), thereby contributing to reductions in blood pressure. Current models of the RAS are based on the concept that the two enzymes counterbalance each other.