Immune Response to Infectious Diseases CHAPTER 17 emergence of a new subtype of influenza whose HA and pos sibly also NA are considerably different from that of the virus present in a preceding epidemic. The first time a human influenza virus was isolated was in 1934; this virus was given the subtype designation HONI (where H is hemagglutinin and n is neuraminidase). The LoNi subtype persisted until 1947, when a major antigenic shift generated a new subtype, HINI, which supplanted the previous subt and became prevalent worldwide until 957, when H2N2 emerged. The H2N2 subtype prevailed for the next decade and was replaced in 1968 by H3N2 Antigenic shift in 1977 saw the re-emergence of HIN1. The most recent antigenic shift, in 1989, brought the re-emergence of H3N2, which remained dominant throughout the next several years. o 1 um a 3 However, an HiNi strain re-emerged in Texas in 1995, and current influenza vaccines contain both h3n2 and hini strains. With each antigenic shift, hemagglutinin and neu FIGURE 17-3 Electron micrograph of influenza virus reveals roughly raminidase undergo major sequence changes, resulting in spherical viral particles enclosed in a lipid bilayer with protruding major antigenic variations for which the immune system hemagglutinin and neuraminidase glycoprotein spikes. Courtesy of lacks memory. Thus, each antigenic shift finds the population G Murti, Department of Virology, St Jude Childrens Research Hospital, immunologically unprepared, resulting in major outbreaks of nfluenza, which sometimes reach pandemic proportions ferent strands of single-stranded RNA (ssRNA) associated luting Matrix protein with protein and Rna polymerase(Figure 17-4). Each RNA strand encodes one or more different influenza proteins Lipid bilayer Three basic types of influenza(A, B, and C), can be distin- guished by differences in their nucleoprotein and matrix pro- teins. Type A, which is the most common, is responsible for the major human pandemics. Antigenic variation in hemagglu tinin and neuraminidase distinguishes subtypes of type A in- fluenza virus. According to the nomenclature of the World &/MI. M2WE Health Organization, each virus strain is defined by its animal NAw host of origin(specified, if other than human), geographical NP origin, strain number, year of isolation, and antigenic descrip HAWAWNVM tion of HA and Na Table 17-2). For example, A/Sw/lowa/ PAVMMMA 15/30(HIN1) designates strain-A isolate 15 that arose in swine PBI in lowa in 1930 and has antigenic subtypes 1 of HA and NA. WAS Notice that the H and N spikes are antigenically distinctin thes two strains. There are 13 different hemagglutinins and 9 neu raml inidases among the type a influenza viruses &s. The distinguishing feature of influenza virus is its vari- ity. The virus can change its surface antigens so com pletely that the immune response to infection with the virus 01020304050 that caused a previous epidemic gives little or no protection Nanometers against the virus causing a subsequent epi genic variation results primarily from changes in the hemag. FIGURE 17-4 Schematic representation of influenza structure. The glutinin and neuraminidase spikes protruding from the viral envelope is covered with neuraminidase and hemagglutinin spikes In- envelope(Figure 17-5). Two different mechanisms generate side is an inner layer of matrix protein surrounding the nucleocapsid antigenic variation in HA and NA: antigenic drift and anti- which consists of eight ssRNA molecules associated with nucleopro genic shift. Antigenic drift involves a series of spontaneous tein. The eight RNA strands encode ten proteins: PBl, PB2, PA, HA point mutations that occur gradually, resulting in minor (hemagglutinin), NP(nucleoprotein), NA(neuraminidase),M1, M2 changes in HA and NA Antigenic shift results in the sudden NSl, and NS2ferent strands of single-stranded RNA (ssRNA) associated with protein and RNA polymerase (Figure 17-4). Each RNA strand encodes one or more different influenza proteins. Three basic types of influenza (A, B, and C), can be distin￾guished by differences in their nucleoprotein and matrix pro￾teins. Type A, which is the most common, is responsible for the major human pandemics. Antigenic variation in hemagglu￾tinin and neuraminidase distinguishes subtypes of type A in￾fluenza virus. According to the nomenclature of the World Health Organization, each virus strain is defined by its animal host of origin (specified, if other than human), geographical origin, strain number, year of isolation, and antigenic descrip￾tion of HA and NA (Table 17-2). For example, A/Sw/Iowa/ 15/30 (H1N1) designates strain-A isolate 15 that arose in swine in Iowa in 1930 and has antigenic subtypes 1 of HA and NA. Notice that the H and N spikes are antigenically distinct in these two strains. There are 13 different hemagglutinins and 9 neu￾raminidases among the type A influenza viruses. The distinguishing feature of influenza virus is its vari￾ability. The virus can change its surface antigens so com￾pletely that the immune response to infection with the virus that caused a previous epidemic gives little or no protection against the virus causing a subsequent epidemic. The anti￾genic variation results primarily from changes in the hemag￾glutinin and neuraminidase spikes protruding from the viral envelope (Figure 17-5). Two different mechanisms generate antigenic variation in HA and NA: antigenic drift and anti￾genic shift. Antigenic drift involves a series of spontaneous point mutations that occur gradually, resulting in minor changes in HA and NA. Antigenic shift results in the sudden emergence of a new subtype of influenza whose HA and pos￾sibly also NA are considerably different from that of the virus present in a preceding epidemic. The first time a human influenza virus was isolated was in 1934; this virus was given the subtype designation H0N1 (where H is hemagglutinin and N is neuraminidase). The H0N1 subtype persisted until 1947, when a major antigenic shift generated a new subtype, H1N1, which supplanted the previous subtype and became prevalent worldwide until 1957, when H2N2 emerged. The H2N2 subtype prevailed for the next decade and was replaced in 1968 by H3N2. Antigenic shift in 1977 saw the re-emergence of H1N1. The most recent antigenic shift, in 1989, brought the re-emergence of H3N2, which remained dominant throughout the next several years. However, an H1N1 strain re-emerged in Texas in 1995, and current influenza vaccines contain both H3N2 and H1N1 strains. With each antigenic shift, hemagglutinin and neu￾raminidase undergo major sequence changes, resulting in major antigenic variations for which the immune system lacks memory. Thus, each antigenic shift finds the population immunologically unprepared, resulting in major outbreaks of influenza, which sometimes reach pandemic proportions. Immune Response to Infectious Diseases CHAPTER 17 393 Matrix protein Lipid bilayer Hemagglutinin Neuraminidase Nucleocapsid NS1, NS2 M1, M2 PB2 PB1 PA HA NP NA 0 10 20 30 40 50 Nanometers FIGURE 17-3 Electron micrograph of influenza virus reveals roughly spherical viral particles enclosed in a lipid bilayer with protruding hemagglutinin and neuraminidase glycoprotein spikes. [Courtesy of G. Murti, Department of Virology, St. Jude Children’s Research Hospital, Memphis, Tenn.] FIGURE 17-4 Schematic representation of influenza structure. The envelope is covered with neuraminidase and hemagglutinin spikes. In￾side is an inner layer of matrix protein surrounding the nucleocapsid, which consists of eight ssRNA molecules associated with nucleopro￾tein. The eight RNA strands encode ten proteins: PB1, PB2, PA, HA (hemagglutinin), NP (nucleoprotein), NA (neuraminidase), M1, M2, NS1, and NS2. O.1 m