Host nutritional status: the neglected virulence factor

Abstract

The emergence of new infectious diseases and old diseases with new pathogenic properties is a burgeoning worldwide problem. Severe acute respiratory syndrome (SARS) and acquired immune deficiency syndrome (AIDS) are just two of the most widely reported recent emerging infectious diseases. What are the factors that contribute to the rapid evolution of viral species? Various hypotheses have been proposed, all involving opportunities for virus spread (for example, agricultural practices, climate changes, rainforest clearing or air travel). However, the nutritional status of the host, until recently, has not been considered a contributing factor to the emergence of infectious disease. In this review, we show that host nutritional status can influence not only the host response to the pathogen, but can also influence the genetic make-up of the viral genome. This latter finding markedly changes our concept of host-pathogen interactions and creates a new paradigm for the study of such phenomena.

Figure 1

Selection of new viral quasispecies with increased virulence in a nutritionally stressed host. A viral quasispecies is used to infect two different populations of mice: nutritionally adequate or nutritionally deficient. Note that the consensus sequence of the viral quasispecies is avirulent (blue circles) although a virulent genotype (orange circles) is present in the mix in a very small amount and is not detectable by sequencing. Nutritionally adequate mice infected with the viral quasispecies do not develop pathology and sequencing of the virus genome confirms that the virus remains the avirulent genotype. Nutritionally deficient mice infected with viral quasispecies develop severe pathology. Isolation and sequencing of virus recovered from the nutritionally deficient host demonstrates selection of a new consensus sequence with a virulent genotype (orange circles). Once the virulent genotype becomes dominant in the viral quasispecies, even nutritionally adequate mice will develop severe pathology.