Molecular variability of influenza virus

Abstract

Gripa je kozmopolitski rasprostranjena virusna bolest koja većinom zahvaća dišne putove čovjeka. Razlikujemo tri roda virusa gripe A, B i C, od kojih je tip A odgovoran za većinu simptoma koje se pripisuju gripi. Unatoč maloj veličini genoma i nekolicini gena koje kodira, ovaj virus pokazuje veliku varijabilnost koja ga čini nepredvidljivim. Promjenljiva priroda ovih virusa omogućava im formiranje novih varijanti sposobnih zaobići imunosnu obranu čovjeka. Godišnje epidemije gripe rezultat su mutacija površinskih antigena HA i NA (antigensko skretanje). Zbog segmentiranog genoma, formiranje novih varijanata virusa gripe A može se ostvariti i preko pseudorekombinacija segmenata različitih sojeva (antigenska izmjena). Ovaj rijetki događaj može rezultirati pandemijom gripe, kojih je tijekom prošlih 100 godina bilo pet. Kako bi pokušali smanjiti opasnost pojave nove pandemije potrebno je razumjeti molekularne mehanizme koji stoje iza procesa koji dovode do varijabilnosti, a ti su mehanizmi pojašnjeni detaljnije u ovom radu kao i primjeri iz prošlosti. Virus gripe koji bi imao potencijal izazivanja pandemije mora imati sposobnost replikacije u čovjeku, na ovojnici nove HA i/ili NA antigene, te se mora efektivno rasprostranjivati u ljudskoj populaciji. Brza evolucija virusa gripe naglašava važnost postojanja nadzora, kako bi se na vrijeme prepoznali novih sojevi. Trenutne metode prevencije i liječenja gripe uključuju cijepljenje i korištenje antivirusnih lijekova.Influenza is a widespread viral disease that mainly affects the human respiratory system. The influenza virus is divided into three types A, B and C. Type A virus is the most virulent human pathogen among the three types and causes the severest disease. Despite the small size of the genome and the few genes encoded by it, this virus shows a high degree of variability that makes it unpredictable. The changeable nature of these viruses allows them to create new variants capable of bypassing human immune defence. Annual flu epidemics are the result of mutations in genes for surface antigens HA and NA (antigenic drift). The formation of new variants of influenza A virus can also be achieved through reassortment of the segmented genome (antigenic shift). Such changes are often associated with the occurrence of pandemics, which happened during the past 100 years five times. In order to reduce the risk of emergence of new pandemics, it is necessary to understand the molecular mechanisms behind the processes that lead to variability. These mechanisms are further explained in this paper, as well as examples from the past. The influenza virus that would have the potential to cause a pandemic must have the ability to replicate in humans, new HA or NA antigen present on the surface and the ability to be effectively transmitted. The rapid evolution of influenza viruses highlights the importance of surveillance in identifying novel circulating strains. The current methods of prevention and treatment of influenza include vaccination and the use of antiviral dru