Virus adaptation by manipulation of host's gene expression

Abstract

Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.

Figure 1. Symptoms developed 21 dpi by plants infected with ancestral and evolved TEV.

(A) A mock-inoculated plant is shown at the left. Plants inoculated with the ancestral virus (TEV) show milder symptoms than plants inoculated with the evolved virus (TEV-At17). (B) Details of a healthy leaf from control plants (Mock), a leaf infected with the ancestral virus showing light vein clearing (TEV), and a leaf infected with the evolved virus (TEV-At17) and showing vein clearing and deformation.

Figure 2. Scatter plot of expression patterns of 12,120 genes between TEV- versus TEV-At17-infected plants.

Expression data were normalized by the median value obtained for the mock-inoculated plants. Green and red spots represent genes whose expression was significantly down- and up-regulated, respectively, in plants infected with TEV-At17 relative to those infected with the ancestral TEV virus. Black spots correspond to genes whose expression did not differentially respond to the infection of each viral genotype.

Figure 3. Self-organization maps (SOMs) showing different patterns of gene expression.

Gene expression patterns for control (Mock), TEV-infected and TEV-At17-infected plants are organized into SOMs (labeled as 1 to 4 on panels A and B). The actual number of genes belonging to each SOM category is indicated below the corresponding label (in parenthesis). Green ranges are used to represent different levels of down-regulation relative to the control uninfected plants; red ranges are used to represent different magnitudes of up-regulation relative to uninfected plants. The brighter the color, the larger the difference in gene expression. (A) Plant genes whose expression is up-regulated upon infection with TEV-At17 compared with plants infected with the ancestral TEV. (B) Genes whose expression is down-regulated in plants infected with TEV-At17 compared with plants infected with the ancestral TEV.