Wednesday, May 13, 2009

Influenza Virus - Genetic Infos Exchange


Influenza, which has been recognized as a human disease for centuries, is notable because it causes a typical acute infection and elicits a strong immune response but continues to occur regularly. Influenza can occur in many nations almost simultaneously (pandemics) with serious consequences. After more than 65 years of research, we now have some reasonable ideas about why this virus causes epidemics annually and pandemics at frequent intervals. Influenza virus not only infects humans, but also infects several other animals in a complex cycle of dissemination. Epidemiologists can classify a given influenza A virus by its antigenic composition, usually by serologic testing of the two envelope proteins hemagglutinin (HA or H) and neuraminidase (NA or N). A common simplification in nomenclature is to refer to combinations of H and N as HxNy (currently x ranges from 1 to 15, and y ranges from 1 to 9), e.g., H1N1 or H5N2. At least 15 subtypes of viral hemagglutinin are known in viruses that infect birds. Three of these subtypes are present in viruses that can infect humans (H1N1, H2N2 and H3N2), and at least two can infect pigs, horses and aquatic mammals. For the past 25 years, H3N2 and H1N1 viruses have cocirculated in humans. In 1997 and 1999, the avian viruses H5N1 and H9N2, respectively, were transmitted directly to humans. The contribution of these serotypes to human disease is under close scrutiny. Viruses can be transmitted to completely new host species that have not experienced any prior infection. Usually host defenses stop the new infection before any replication and adaptation can take place. On rare occasions, a novel population of viruses arises in the new host. Past interspecies infections can occasionally be detected by sequence analysis. The data provide a glimpse of the rather amazing and unpredictable paths of virus evolutions.
This following picture will show how Influenza A Virus do the replication process :

Genetic information is exchanged by recombination or by reassortment of genome segments. In one step, recombination creates new combinations of many mutations that may be essential for survival under selective pressures. This process allows the constructions of viable genomes from debilitated ones and avoids Muller's ratchet. Recombination occurs when the polymerase changes templates (copy choice) during replication or when nucleic acid segments are broken or rejoined. The former mechanism is common among RNA viruses, whereas the latter is more typical of double-stranded DNA virus recombination. Another mechanism for exchange of genetic information is reassortment among genomic segments when cells are coinfected with segmented RNA viruses. Viral infections occur as host defenses are modulated or bypassed. Those infections that actively suppress the immune response have a marked effect upon concurrent or subsequent infections of the same host by very different viruses.
Conversely, activation of host defenses by one viral infection can impair subsequent infection by a different virus. The existence of such multifactorial interchange among diverse viruses reinforces the idea that selection acts not only on one population of viruses, but also on interacting populations of different viruses.
Reassortment is when gene segments from two different viruses get mixed and repackaged into the same virion. This is possible when two different viruses infect the same cell at the same time. This can occur in all three types of influenza but will not occur between the different types.

Antigenic Shift
Antigenic shift is a specific kind of reassortment where the HA or NA gene segment from two different strains are switched. This typically happens when an avian strain and human strain infect the same pig cell.

Antigenic Drift
Antigenic drift refers to point mutations (single mutations) in the genome and can lead to changes in the HA or NA proteins. The RNA-dependent RNA polymerase is not as accurate as DNA-dependent RNA polymerase, so these mutations occur often.

  • Gibbs, M.J., and G.F. Weiller. 1999. Evidence that a plant virus switched hosts to infect a vertebratae and then recombined with a vertebrate-infecting virus. Proc. Natl. Acad. Sci. USA. 96:8022-8027.
  • Dimmock, N.J. et al. 2007. Introduction to modern virology, 6th ed. Blackwell Publishing.


nyu said...

sugoi na bun-chan... you get to study all that headache-inducing stuffs.. :))

bunga (馬莎莉) said...

hihihi...seems can be a "good" trigger for having a bad headache rite, Nyu?
well, yeah^^...