Mechanisms of viral emergence

Domingo, Esteban

Mechanisms of viral emergence Vet. Res. (2010) 41:38 and re-emergences of human viral diseases, that have amounted to about one per year during the last decades, have been associated with RNA viruses that display active recombination or reassortment. As examples, several recent poliomyelitis outbreaks have been related to viruses generated by recombination between attenuated vaccine polioviruses and other circulating enteroviruses [75] . As an historical event, the coronavirus mouse hepatitis virus appears to have acquired its hemagglutinin-esterase gene by recombination with an influenza type C virus [46] . Also, the alphavirus Western equine encephalitis virus probably resulted from an ancient recombination between a Sindbis-like and a Easter-equine encephalitis-like virus (reviewed in [87] ). The emergence of the SARS coronavirus around 2002 probably involved the transfer of the virus from a bat to a carnivore (probably a civet cat); contact with civets may have facilitated the human outbreak. The human ACE2 receptor-binding sequences used by the human SARS coronavirus may have been acquired by recombination with a preexisting group 1 human coronavirus [45] . In this, and in the other cases in which recombination played a role in the generation of a new pathogen, selection of virus variants for a more efficient replication in the new host (for receptor use or other) probably took place [91] . Genome segment reassortment is a major evolutionary force for some viruses with a segmented genome, the most studied case being reassortments in the influenza type A viruses. Reassortants that have acquired the hemagglutinin and/or neuraminidase genes from viruses of some animal reservoirs (notably birds or swine) have been associated with the major human influenza pandemics such as the Spanish influenza of 1918 (H1N1 virus), the Hong Kong influenza of 1968 (H3N2 virus) or the pandemics of 2009 (H1N1 virus) [35, 66, 74] . Such viruses acquired a selective advantage relative to previously circulating influenza viruses because the new hemagglutinin and/or neuraminidase surface antigens were not recognized (or were only poorly recognized) by the neutralizing antibodies present in the human population. The acquisition of new genome segments that produce a change in antigenic specificity is termed antigenic shift. The gradual antigenic modification undergone by the virus as it circulates in the human population is termed antigenic drift. The latter is linked to point mutations that affect the antigenic determinants, and can be regarded as the fitness adjustment by mutation as the virus explores new environments (some of which include anti-influenza antibodies) following a reassortment event. Drastic and gradual versions of antigenic variation are not exclusive of influenza virus, and they have been amply recognized as a major factor in the adaptation of viruses to host organisms endowed with an immune system [48, 67] . Viruses are undoubtedly subjected to selective constraints additional to the several components of an immune response, and some of them probably have not even been identified. Multiple constraints contribute to shape the genomic compositions of the viral populations as they complete successive life cycles. Mutation, recombination and reassortment can produce new viral forms, a minority of which might be competent to replicate in a new environment. There is evidence that a true recombinant hemagglutinin might have been one of the virule