Citrus tristeza virus: A large RNA virus with complex biology turned into a valuable tool for crop protection

From a research standpoint, CTV is one of the most challenging viruses to handle, which is due to the large size of its RNA genome, the fragile nature of the virions that have a shape of long flexuous thread-like filaments (Fig 1B and Fig 1C), and a narrow host range limited to slow-growing Citrus species in which the virus primarily infects phloem-associated cells. CP, major coat protein; CPm, minor coat protein; CTV, citrus tristeza virus; GFP, green fluorescent protein; HEL, helicase-like domain; HSP70h, HSP70 homolog; L1, L2, papain-like leader protease domains; LMT1, low-molecular-weight tristeza RNA 1; LMT2, low-molecular-weight tristeza RNA 2; MT, methyltransferase-like domain; ORF, open reading frame; RdRp, an RNA-dependent RNA polymerase; sg, subgenomic; SIE, superinfection exclusion; WT, wild type. https://doi.org/10.1371/journal.ppat.1008416.g001 CTV is among viruses with largest RNA genomes CTV possesses a 19.3 kilobase (kb) positive-stranded RNA genome, which is nearly twice as large as the average sized RNA virus genome of 10 kb [3]. In a broader perspective, the size of the CTV genome could be compared with that of animal nidoviruses whose genomes are represented by positive-sense RNA molecules ranging between 20 and 41.1 kb in size [4]. Besides the size, the genome of CTV that encodes 12 open reading frames (ORFs) has other peculiar features, among which are the presence of two sets of duplicated and diverged genes, e.g., the genes for the papain-like leader proteases and the genes for the major and minor coat proteins as well as the presence of a gene closely related to the genes coding for the cellular heat shock proteins in the HSP70 family and of three genes coding for suppressors of host RNA silencing [3, 5] (Fig 1C). The most 5’-proximal ORF, ORF1a, is expressed from the genomic RNA resulting in production of a 349-kDa protein that contains a tandem of two leader protease domains plus methyltransferase-like and helicase-like domains.