Chapter 187

### Definition

Influenza is an acute respiratory illness caused by infection with influenza viruses. The illness affects the upper and/or lower respiratory tract and is often accompanied by systemic signs and symptoms such as fever, headache, myalgia, and weakness. Outbreaks of illness of variable extent and severity occur nearly every year. Such outbreaks result in significant morbidity rates in the general population and in increased mortality rates among certain high-risk patients, mainly as a result of pulmonary complications.

### Etiologic Agent

Influenza viruses are members of the Orthomyxoviridae family, of which influenza A, B, and C viruses constitute three separate genera. The designation of influenza viruses as type A, B, or C is based on antigenic characteristics of the nucleoprotein (NP) and matrix (M) protein antigens. Influenza A viruses are further subdivided (subtyped) on the basis of the surface hemagglutinin (H) and neuraminidase (N) antigens (see below); individual strains are designated according to the site of origin, isolate number, year of isolation, and subtype—for example, influenza A/California/07/2009 (H1N1). Influenza A has 16 distinct H subtypes and 9 distinct N subtypes, of which only H1, H2, H3, N1, and N2 have been associated with epidemics of disease in humans. Influenza B and C viruses are similarly designated, but H and N antigens from these viruses do not receive subtype designations, since intratypic variations in influenza B antigens are less extensive than those in influenza A viruses and may not occur with influenza C virus.

Influenza A and B viruses are major human pathogens and the most extensively studied of the Orthomyxoviridae. Type A and type B viruses are morphologically similar. The virions are irregularly shaped spherical particles, measure 80–120 nm in diameter, and have a lipid envelope from the surface of which the H and N glycoproteins project (Fig. 187-1). The hemagglutinin is the site by which the virus binds to sialic acid cell receptors, whereas the neuraminidase degrades the receptor and plays a role in the release of the virus from infected cells after replication has taken place. Influenza viruses enter cells by receptor-mediated endocytosis, forming a virus-containing endosome. The viral hemagglutinin mediates fusion of the endosomal membrane with the virus envelope, and viral nucleocapsids are subsequently released into the cytoplasm. Immune responses to the H antigen are the major determinants of protection against infection with influenza virus, while those to the N antigen limit viral spread and contribute to reduction of the infection. The lipid envelope of influenza A virus also contains the M proteins M1 and M2, which are involved in stabilization of the lipid envelope and in virus assembly. The virion also contains the NP antigen, which is associated with the viral genome, as well as three polymerase (P) proteins that are essential for transcription and synthesis of viral RNA. Two nonstructural proteins function as an interferon antagonist and posttranscriptional regulator (NS1) and a nuclear export factor (NS2 or NEP).

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