The first of these, caused by point mutations in the genes encoding the two major viral surface glycoproteins—hemagglutinin and neuraminidase—is called antigenic drift. Every 2–3 years a variant flu virus arises with mutations that allow it to evade neutralization by the antibodies present in the population. Other mutations may affect epitopes in viral proteins that are recognized by T cells, particularly CD8 cytotoxic T cells, with the consequence that cells infected with the mutant virus also escape destruction. People immune to the old flu virus are thus susceptible to the new variant, but because the changes in the viral proteins are relatively minor, there is still some crossreaction with antibodies and memory T cells produced against the previous variant, and most of the population still has some level of immunity. Thus, epidemics resulting from antigenic drift are typically mild.
Antigenic changes in influenza virus that result from reassortment of the segmented RNA genome are known as antigenic shift, and result in major changes in the hemagglutinin expressed by the virus. Antigenic shifts cause global pandemics of severe disease, often with substantial mortality, because the new hemagglutinin is recognized poorly, if at all, by antibodies and T cells
Fig. 13.22 Two types of variation allow repeated infection with type A influenza virus. neutralizing antibody that mediates protective immunity is directed at the viral surface protein hemagglutinin (H), which is responsible for viral binding to and entry into cells. antigenic drift (left panels) involves the emergence of point mutants with altered binding sites for protective antibodies on the hemagglutinin. the new virus can grow in a host that is immune to the previous strain of virus, but as t cells and some antibodies can still recognize epitopes that have not been altered, the new variants cause only mild disease in previously infected individuals. antigenic shift (right panels) is a rare event involving the reassortment of the segmented Rna viral genomes of two different influenza viruses, probably in a bird or a pig. these antigen-shifted viruses have large changes in their hemagglutinin, and therefore t cells and antibodies produced in earlier infections are not protective. these shifted strains cause severe infection that spreads widely, causing the influenza pandemics that occur every 10–50 years. there are eight Rna molecules in each viral genome, but for simplicity only three are shown.
directed against the previous variant. Antigenic shift is due to reassortment of the segmented RNA genome of the human influenza virus and animal influenza viruses in an animal host, in which the hemagglutinin gene from the animal virus replaces the hemagglutinin gene in the human virus (see Fig. 13.22).
Hepatitis C virus (HCV) is an RNA virus that can cause both acute and chronic infections of the liver. It is the most common cause of bloodborne chronic infection in the United States, and the leading viral cause of liver cirrhosis. As with influenza virus, HCV has a high capacity for mutation of immune epitopes that allow it to evade elimination. However, unlike influenza, the viral surface glycoprotein responsible for binding of HCV to hepatocytes (E2, which binds CD81) presents a difficult target against which to produce effective neutralizing antibodies, due both to its heavy glycosylation in the region of CD81 binding and its high rate of mutation. Antibody responses against HCV are therefore of limited effectiveness. Similarly, high rates of mutation of Tcell epitopes select for escape variants of HCV that evade cytolytic Tcell responses. Finally, there is evidence that HCV also expresses factors that subvert the function of dendritic cells, thereby impairing the induction of Tcell immunity.
13-23 DNA viruses use multiple mechanisms to subvert NK-cell and CTL responses.