Immune Evasion by Viruses

Viruses have evolved numerous mechanisms for evading host immunity (Table 15-3).

• Viruses can alter their antigens and are thus no longer targets of immune responses. The antigens affected are most commonly surface glycoproteins that are recognized by antibodies, but T cell epitopes may also undergo variation. The principal mechanisms of anti-genic variation are point mutations and reassortment of RNA genomes (in RNA viruses), leading to antigenic drift and antigenic shift. These processes are of great importance in the spread of influenza virus. The two major antigens of the virus are the trimeric viral hem-agglutinin (the viral "spike" protein) and neuramini-dase. Viral genomes undergo mutations in the genes that encode these surface proteins, and the variation that occurs as a result is called antigenic drift. Influenza viruses that normally inhabit different host species can recombine in host cells, and these reassorted viruses can differ quite dramatically from prevalent strains (Fig. 15-8). These reassortment processes result in a major change in antigenic structure called antigenic shift, which creates distinct viruses such as the avian flu or the swine flu viruses. Because of antigenic variation, a virus may become resistant to immunity generated in the population by previous infections. The influenza pandemics that occurred in 1918, 1957, and 1968 were due to different strains of the virus, and the H1N1 pandemic of 2009 was due to a strain in which the strands of the RNA genome were reassorted among strains endemic in pigs, fowl, and humans. Subtler viral variants arise more frequently. There are so many sero-types of rhinovirus that specific immunization against the common cold may not be a feasible preventive strategy. Human immunodeficiency virus 1 (HIV-1), the virus that causes AIDS, is also capable of tremendous antigenic variation (see Chapter 20). In these situations, prophylactic vaccination may have to be directed against invariant viral proteins.

• Some viruses inhibit class I MHC-associated presentation of cytosolic protein antigens. Viruses make a variety of proteins that block different steps in antigen processing, transport and presentation (Fig. 15-9). Inhibition of antigen presentation blocks the assembly and expression of stable class I MHC molecules and the display of viral peptides. As a result, cells infected by such viruses cannot be recognized or killed by CD8+ CTLs. However, it is difficult to prove that the viral genes encoding proteins that inhibit antigen presentation are actually virulence genes, required for the infectivity or pathogenicity of the viruses. NK cells may have evolved as an adaptation to this viral evasion strategy because NK cells are activated by infected cells, especially in the absence of class I MHC molecules. There is emerging evidence that some viruses may produce proteins that act as ligands for NK cell inhibitory receptors and thus inhibit NK cell activation. These are excellent examples of the constant

TABLE 15-3 Mechanisms of Immune Evasion by Viruses

Mechanism of Immune Evasion

Examples

Antigenic variation

Influenza, rhinovirus, HIV

Inhibition of antigen processing Blockade of TAP transporter Removal of class I molecules from the ER

Herpes simplex Cytomegalovirus

Production of cytokine receptor homologues

Vaccinia, poxviruses (IL-1, IFN-y) Cytomegalovirus (chemokine)

Production of immunosuppressive cytokine

Epstein-Barr (H-10)

Infection and death or functional impairment of immune cells

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