Impact of RNA Virus Evolution on Quasispecies Formation and Virulence

Abstract

RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.

Keywords: RNA viruses; plaque phenotype; quasispecies; spontaneous mutations; virulence.

Figure 1

(A) The structure of the picornavirus (30 nm). The viral structural proteins (VP1–VP4) are depicted. (B) Schematic representation of the EV-A71 genome (7.4 Kb). The Open Reading Frame (ORF) contains the structural viral protein P1 which is cleaved to yield VP1, VP2, VP3 and VP4 and non-structural viral proteins P2 (cleaved to yield 2A, 2B and 2C) and P3 (cleaved to yield 3A, 3B, 3C and 3D). The 3′-NTR end of the genome contains the poly (A) tail.

Figure 2

(A) The virion of the flavivirus (40–60 nm) is illustrated highlighting the position of the E dimers (E1 and E2), capsid protein and RNA genome (B) Schematic representation of the Flavivirus structure and genome (11 kb). The position of the 5′-NTR and the 3′-NTR are shown. The Open Reading Frame (ORF) contains the structural viral proteins (C, prM and E) and the non-structural viral proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5).

Figure 3

(A) The alphavirus structure depicting the position of the E protein (E1 and E2 trimers), capsid protein and the genomic RNA. (B) The genome structure of the alphavirus is represented showing the 5′ and 3′ untranslated regions. Open boxes represent the non-structural proteins (NSP1, NSP2, NSP3 and NSP4) and structural proteins (CP, E3, E2, 6K and E1).

Figure 4

(A) Schematic representation of mature Ebola virion consisting of two main components—the nucleocapsid and envelope. The matrix comprising the virion proteins VP24 and VP40 is located between the nucleocapsid and envelope. Glycoprotein (GP) spikes are located on the surface of the envelope (B) The genome contains 7 genes which encode the six structural proteins and one non-structural protein [79]. The gene order is 5′-NTR-NP (nucleoprotein)-VP35-VP40 (Major matrix protein)-GP/sGP (Glycoprotein)-VP30-VP24 (Minor matrix protein)-RNA-dependent RNA polymerase (l)-3′-NTR [80].

Figure 5

(A) Schematic representation of the coronavirus structure and the spike protein features. The virion membrane is enriched with membrane proteins (S, M, E and HE dimer). (B) The 31 kb genome and the position of multiple ORFs are illustrated.

Figure 6

The predicted MERS-CoV spike precursor glycoprotein (encoded by the S gene).

Figure 7

(A) A paramyxovirion of 150 nm showing the important viral structural components (F protein, M protein and HN/G/H glycoprotein spikes) (B) Paramyxovirus genome containing six genes in the order—N, P/C/V, M, F, H and L.

Figure 8

(A) Illustration of the pneumovirus structure showing various components of the nucleocapsid and genomic structure (B) The negative strand of the unsegmented genome of 13.2–15.3 kb codes for structural proteins such as the nucleocapsid (N) and RNA-dependent RNA polymerase complex (L), phosphoprotein (P), cysteine rich protein (V), the matrix (M) protein, the three surface glycoprotein fusion proteins (F), glycosylated attachment protein (G), short hydrophobic protein (SH) followed by nonstructural proteins such as NS-1 and NS-2 that modulate host responses.

Figure 9

(A) The schematic illustration of influenza A virion with the two major glycoproteins displayed on the surface—hemagglutinin (HA), neuraminidase (NA). (B) The viral RNA genome of 12–15 kb consists of eight single-stranded RNA segments.

Figure 10

(A) Schematic representation of the hepadnavirus structure bearing common structural proteins are portrayed together with the DNA genome (B) The overlapping ORFs, negative sense viral RNA and positive RNA strand.