The virus as metabolic engineer

Abstract

Recent genome-wide screens of host genetic requirements for viral infection have reemphasized the critical role of host metabolism in enabling the production of viral particles. In this review, we highlight the metabolic aspects of viral infection found in these studies, and focus on the opportunities these requirements present for metabolic engineers. In particular, the objectives and approaches that metabolic engineers use are readily comparable to the behaviors exhibited by viruses during infection. As a result, metabolic engineers have a unique perspective that could lead to novel and effective methods to combat viral infection.

Figure 1. A comparison between viruses and metabolic engineers in terms of objectives, resources, constraints and methods

The viral properties are shown in the middle column and the metabolic engineer in the right column.

Figure 2. Host genes in central metabolism that play an important role in viral infection

A central metabolic network is shown, where each arrow represents a reaction that is denoted by the corresponding Enzyme Commission (E.C.) number. Reactions that were found in one of several screens for host genetic requirements in viral infection are highlighted with a grey box, and the genes are noted in parentheses (human genes are all caps, and E. coli genes are italicized). A table is inset which provides more information about the highlighted genes, including which screen identified them as essential. HIV (Br) refers to [26], HIV (Ko) refers to[27], HIV (Zh) refers to [29], Flu (Br) refers to [30], Flu (Ko) refers to [33], Flu (Ka) refers to [32], Dengue (Se) refers to [36], Lambda (MA) refers to [74].

Figure 3. A Venn diagram categorizing E. coli genes required for optimal lambda phage infection as determined using forward or reverse genetics

The genes in the right circle were identified by several groups over many years using reverse genetics. The genes in the left circle were identified in a forward genetic screen recently performed by our lab [74]. Genes highlighted in grey are found in either the Feist flux balance model [78]or the Covert regulated flux balance model of E. coli [79].