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INTRODUCTION

Host defenses against viruses fall into two major categories: (1) nonspecific, of which the most important are interferons and natural killer (NK) cells and (2) specific, including both antibody and cell-mediated immunity. Interferons are an early, first-line defense, whereas humoral immunity and cell-mediated immunity are effective only later because it takes several days to induce the humoral and cell-mediated arms of the immune response.

A description of how viruses evade our host defenses appears in Chapter 32.

NONSPECIFIC DEFENSES

Evidence for the importance of interferons includes (1) people who have a defective interferon response are prone to frequent and severe viral infections; (2) those who have an auto-immune response to interferon, i.e., produce antibody to it are also predisposed to severe viral infections; (3) several viruses, e.g., SARS, coronavirus-2, and influenza virus synthesize proteins that inhibit either the synthesis or action of interferon.

1. Alpha & Beta Interferons

Alpha and beta interferons are a group of proteins produced by human cells after viral infection (or after exposure to other inducers). They inhibit the growth of viruses by blocking the synthesis of viral proteins. They do so by two main mechanisms: One is a ribonuclease that degrades mRNA, and the other is a protein kinase that inhibits protein synthesis.

Interferons are divided into three types based on the cell of origin, namely, leukocyte, fibroblast, and lymphocyte. They are also known as alpha, beta, and gamma interferons, respectively. Alpha and beta interferons, collectively known as type I interferon, are induced by viruses, whereas gamma (T cell, immune) interferon, known as type II interferon, is induced by antigens and is one of the effectors of cell-mediated immunity (see Chapter 58). The following discussion of alpha and beta interferons focuses on the induction and action of their antiviral effect (Figure 33–1).

FIGURE 33–1

Induction and action of interferon. Left side: Virus infection induces the synthesis of interferon, which then leaves the infected cell. Right side: Interferon binds to the surface receptor of an uninfected cell and induces the synthesis of three new cell-encoded enzymes (antiviral proteins). A new virion enters the cell, but viral replication is inhibited by the interferon-induced antiviral proteins. One of these antiviral proteins is a ribonuclease that degrades mRNA and another is a protein kinase that phosphorylates an initiation factor that inhibits protein synthesis. (Reproduced with permission from Willey J, Sherwood L, Woolverton CJ: Microbiology. 7th ed. New York, NY: McGraw Hill; 2007.)

Lambda (λ) interferon, known as type III interferon, is active against intestinal viruses, especially rotavirus and norovirus. It reduces the long-term persistence of virus in intestinal mucosal cells. The role of lambda interferon in human disease is uncertain and will not be ...

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