The application of genomics to emerging zoonotic viral diseases

Abstract

Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases.

Figure 1. Zoonotic transmission of influenza A virus.

The hemagglutinin of avian influenza A viruses (blue) preferentially bind to oligosaccharides that terminate in sialic acid–α-2,3-Gal (red), whereas the hemagglutinin on human influenza A viruses (green) prefer oligosaccharides that terminate in sialic acid–α-2,6-Gal (orange). Fatal viral pneumonia in humans infected with the H5N1 subtype of avian influenza A viruses is likely due to the ability of these viruses to attach to and replicate in the lower respiratory tract cells, which have sialic acid-α-2,3-Gal terminated saccharides. The horizontal arrows indicate interspecies transmission, including the transmission from an avian or porcine reservoir into the human species. Image credit: Bart Haagmans, Erasmus MC. Original images (left to right, from top to bottom) by Roman Köhler, Alvesgaspar, Anton Holmquist, Joshua Lutz, and CDC.

Figure 2. Zoonotic transmission of SARS-CoV.

Genomic analyses provided evidence that genetic changes in the spike gene of SARS-CoV from bats (left) and civet cats (center) are essential for the animal-to-human transmission (horizontal arrows). Species-to-species genetic variation in the (thus far unidentified) viral receptor in bats and in the angiotensin converting enzyme 2 (ACE2) gene, encoding the SARS-CoV receptor in civet cats and humans also affects the efficiency with which the virus can enter cells (vertical arrows). The SARS-CoV that caused the epidemic evolved a high affinity for both civet (center) and human (right) ACE2 receptors (indicated by the single diagonal and the right side vertical arrow). Image credit: Bart Haagmans, Erasmus MC. Original images (left to right) by Dodoni, Paul Hilton, and Hoang Dinh Nam.