IMMUNOLOGY - Roit A. - Mir 2000

Chapter 16. Antiviral Immunity

VIRAL EVASION STRATEGIES OF IMMUNE CONTROL

Viruses, for their part, possess various mechanisms to protect themselves against antibody recognition. Antigenic variation is the most effective of these: immunodominant regions undergo structural changes in viral Proteins that normally serve as targets for Antibodies. Antigenic variation is observed in HUMAN IMMUNODEFICIENCY VIRUS (HIV) and FOOT-and-Mouth disease virus, as well as in Influenza virus; in the latter case, it is termed antigenic drift (gradual changes) and antigenic shift (abrupt changes) (Fig. 16.9). Humoral Immunity to these viral infections persists only until a new serovariant of the pathogen emerges, which precludes long-term vaccination efficacy.

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Fig. 16.9. The main surface Antigens of the influenza virus are hemagglutinin and neuraminidase. Hemagglutinin (HA) is involved in virus attachment to the host Cell. Antibodies against it exert a protective effect. Antibodies to neuraminidase (NA) are significantly less effective. The surface antigens of the influenza virus can change either gradually (antigenic drift) or abruptly (antigenic shift). As a result of structural Changes in the antigenic determinants of HA, antibodies synthesized against its previous variant become obsolete, thereby triggering new influenza epidemics. The figure schematically depicts influenza virus serovars that have emerged through antigenic shift since 1933. The international nomenclature of influenza virus antigens is based on the designations of hemagglutinin types (H₀, H₁, etc.) and neuraminidase types (N₁, N₂, etc.) expressed On the surface of Viral Particles. Notably, in new serovars that supplant older ones, antigens located within the virion remain unchanged.

Antibodies can remove viral antigens from The Plasma Membrane of a cell via capping. This very mechanism may limit the progression of certain viruses to intracellular persistence. Herpesviruses (human HSV and CMV) encode Glycoproteins that bind IgG via the Fc region—exhibiting FcγR activity—which disrupts Complement activation and blocks the action of antiviral antibodies.

Some viruses (such as Epstein-Barr virus and Adenoviruses) are capable of counteracting the effects of interferons: they produce short RNA segments that compete for protein kinase and somehow suppress the activation of this enzyme. A number of viruses (including adenoviruses and CMV) encode proteins that inhibit The transport of MHC class I molecules to The Cell plasma membrane. This confers a survival advantage to the virus by helping it evade recognition by cytotoxic T Cells.

Certain viruses possess genes encoding proteins homologous to cytokine receptors or even to cytokines themselves. The synthesis and release of these proteins from infected cells—specifically, soluble forms of receptors for IL-1β, TNF, and IFNγ—disrupt the local action of cytokine-mediated defense mechanisms. The Epstein-Barr virus, for instance, encodes a protein homologous to mammalian IL-10 that mimics its activity in vitro. The precise in vivo significance of such viral genome products remains to be fully elucidated.

Data on viral products homologous to antiviral immunity factors are presented in Fig. 16.10.

Fig. 16.10. Viruses employ various pathways to evade host defense systems.