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Influenza viruses are enveloped, −ssRNA viruses with segmented genomes. Influenza A and B viruses are associated with seasonal epidemics, and several pandemics have been caused by influenza A viruses. Virions are transmitted through droplet spread and bind alpha-2,6-linked sialic acids found on the ciliated epithelium of the respiratory tract. Common symptoms include fever, myalgia, sore throat, rhinorrhea, and a nonproductive cough. Children, the elderly, and immunocompromised individuals are at highest risk of secondary bacterial pneumonias. Following receptor binding, the virus undergoes clathrin-mediated endocytosis. The hemagglutinin (HA) protein fuses the viral envelope and endosomal membrane, allowing the release of the ribonucleoproteins. Despite carrying its own RNA-dependent RNA polymerase, viral gene segments enter the nucleus in order to steal the 5′ caps from host mRNAs and splice the smallest two of its transcripts. The virus undergoes assembly at the plasma membrane and buds from the cell. Neuraminidase (NA) cleaves sialic acids upon exit to prevent virion aggregation onto the cell surface. Subtypes of influenza A viruses are categorized by the HA and NA proteins encoded by the virus. Antigenic shifts have led to major pandemics within the last century.

Parasites are complex pathogens, particularly in terms of their antigens, which can vary with life cycle stage and location in the host. Three main biological stages in Trichinella genus were described but it is an oversimplification of the complex Trichinella cycle. Trichinella antigens and immunodominant epitopes have been studied using various strategies requiring immunological reagents or the selection of specific gene targets to be expressed in several systems. Here, we review the Trichinella antigens used for vaccine development and their temporal and spatial variation with the parasite life cycle and in the parasite body. The first antigen studies were devoted to defining antigen profiles reacting with serum samples from various hosts. Trichinella antigens have been classified according to their immunoreactivity with different monoclonal antibodies obtained with various immunization protocols. Based on our knowledge of the Trichinella genome, specific targets have been evaluated. The first fully analyzed immunodominant epitope was s-tyvelose (3,6-dideoxy- d -arabinohexose), a carbohydrate initially found only in the Trichinella genus, but several other linear peptide epitopes have also been described. We discuss their use in vaccine developments taking into account the specific challenge of a foodborne zoonotic parasite. Recently, new data obtained from the use of recombinant antigens offer new challenges for vaccine development, but most studies focus only on rodent models and are far from the scale-up development stage. Adjuvants are of utmost importance in vaccine development and must be well designed to the target host. RNA vaccines may be more appropriate in the future. Ultimately, nematodes with an aborted cycle may be the ideal vaccine candidate in target animals with a local protective immune response and strong immunity, as in natural infection.

Influenza virus (family Orthomyxoviridae) is an enveloped and negative-sense RNA virus. It possesses multiple RNA genomes (ie, eight RNA segments). Unlike other RNA viruses, viral RNA replication occurs in the nucleus. Viral mRNA transcription is primed by capped RNA snatched from cellular mRNAs, a process termed “cap-snatching.” Diverse subtypes of influenza virus are specified by the antigenicity of two envelope proteins, HA and NA (eg, H5N1). Rapid emergence of genetic variants is the salient feature of influenza virus. In addition to incremental changes in antigenicity (antigenic drift), abrupt changes (antigenic shift), which are the result of genetic recombination among eight RNA segments (genetic reassortment), occasionally occur and cause pandemic flu. A nonstructural protein NS1, the major virulence factor, potently blocks the host innate immune response. Yearly vaccination is required for effective protection from seasonal flu.

The family Orthomyxoviridae contains significant pathogens of humans and animals. Virions are spherical to filamentous, about 100 nm in diameter. Genomes are segmented, single-stranded negative-strand RNA. Influenza A virus infects a wide variety of mammals and birds, replicating in the respiratory and/or gastrointestinal tracts. But in birds, highly pathogenic avian influenza viruses (HPAIV) cause severe systemic infections. Transmission of HPAIV to humans is rare, but can result in severe disease with high mortality. Influenza A virus is genetically diverse, a consequence of accumulating and tolerating point mutations, a process called antigenic drift. Influenza viruses can also reassort their segmented genomes to generate novel viruses with altered host range and virulence, a process called antigenic shift. In the early 20th century (1918–19) a particularly lethal strain of influenza A virus infected approximately one-third of the world’s population and caused an estimated 40 million deaths. Although a pandemic of that magnitude has not occurred since, influenza viruses are continuously monitored. In humans, influenza is a mild to severe respiratory tract disease characterized by rapid onset of fever, muscle aches, and fatigue. Severe disease can result from primary viral pneumonia or secondary bacterial infections. Vaccines are manufactured on a yearly cycle to account for the processes of antigenic drift and shift. The ability to manufacture the correct vaccines depends on a robust global tracking system.

Influenza is an ancient and deadly disease which has sickened and killed millions of people in local epidemics and global pandemics. Nowadays, it is common knowledge that influenza is a highly infectious viral illness, but before the discovery of viruses the etiological factor of influenza was not known and, therefore, we had to relay solely on the clinical picture characterized by a sudden onset of high fever, cough, headache, muscle and joint pain, unwell feeling, sore throat, and runny nose. These symptoms were clearly described by Hippocrates roughly 2400 years ago, but historical data on influenza were of difficult interpretation, since these symptoms can be similar to those of other respiratory diseases, therefore not distinctive enough. The word Influenza originated in the 15th century from the Italian language, meaning “influence” since the disease was ascribed to unfavorable astrological influences. A different origin could be the word “influsso” for describing the sweating characteristic of the illness or meaning “influence of the cold.” It was not until 1703 when J. Hugger’s thesis submitted at the University of Edinburgh and named “De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit” that the Englishspoken world directly associated “influenza” with the disease and its symptoms. After that the name influenza and its shorthand “flu” came into more general use.1 The influenza virus was first isolated from pigs in 1930 by Shope and Lewis.2 This seminal discovery was followed by the isolation in ferrets of influenza A virus by Smith, Andrewes, and Laidlaw.3 In 1936, Burnet demonstrated that influenza virus could be grown in chicken embryonated eggs,4 opening the path for the study of the characteristics of the virus. It is estimated that influenza virus infects every year 5–10% of the adult population worldwide and 20–30% of the children. Even though most patients recover from flu symptoms within a short periodand without serious sequelae, the estimates indicate from 3–5 million cases of serious illness and over 250,000 deaths per year. Therefore, due to its medical importance, influenza viruses have been the focus of extensive research to decipher the molecular mechanisms that dominate cell invasion and pathogenesis.

The family Orthomyxoviridae is well known for containing influenza viruses with a segmented RNA genome that is prone to gene reassortment in mixed infections (known as antigenic shift ) resulting in new virus subtypes that cause pandemics, and cumulative mutations (known as antigenic drift ), resulting in new virus strains that cause epidemics. This family also contains infectious salmon anemia virus (ISAV) and tilapia lake virus (TiLV), which are a unique orthomyxoviruses that infect fish and is unable to replicate above room temperature (24°C). This chapter describes the comparative virology of members in the family Orthomyxoviridae in general, helping to understand the emergent teleost orthomyxoviruses, ISAV and TiLV. The most current information on virus–host interactions of the fish orthomyxoviruses, particularly ISAV, as they relate to variations in virus structure, virulence, persistence, host range and immunological aspects is presented in detail.

The orthomyxoviruses include influenza viruses, thogotoviruses, and isaviruses. Influenza A viruses circulate in reservoir of wild aquatic birds, occasionally cause human pandemics, undergo antigenic drift and antigentic shift, and have been used as model viruses to understand many fundamental processes including receptor binding, membrane fusion, protein structure, and adaptive immunity. Influenza A and B viruses contain a hemagglutinin (HA) surface glycoprotein, the dominant surface antigen that promotes receptor binding and membrane fusion during viral entry, and a neuraminidase (NA) glycoprotein, a secondary antigen that has receptor-destroying activity necessary for virus release from infected cells. Influenza C viruses contain a single antigen, the hemagglutinin-esterase-fusion (HEF) protein, which possesses receptor binding, membrane fusion, and virus release functions. The HA and HEF proteins are prototypic, trimeric, structural class I viral fusion proteins with a membrane-distal, immunodominant (and highly variable) receptor-binding head domain and a more highly conserved membrane-proximal, metastable, stalk domain that catalyzes membrane fusion. The tetrameric NA protein has a membrane-distal globular head domain with an antiparallel β-propeller topology and a membrane-proximal coiled-coil stalk. For the influenza A and B viruses, the HA protein is the predominant target for naturally acquired and vaccine-induced adaptive immunity. Recent structural studies of broadly reactive monoclonal antibodies bound to the HA protein, along with complementary immunological experiments, suggest ways to generate “universal” influenza vaccines that are effective after antigenic drift and shift.

As a member of orthomyxoviridae family, influenza viruses are enveloped viruses containing eight RNA segments. The main antigenic determinants of influenza A and B viruses are two surface glycoproteins, the hemagglutinin (H) and the neuraminidase (N). A genetic reassortment between influenza A viruses from different animal hosts may lead to an antigenic shift and thereby increase the risk of a potential pandemic. H1N1 and H3N2 subtypes of influenza A have been circulating all over the world as seasonal influenza since the last H3N2 pandemic in 1968.1 In April 2009, the Centers for Disease Control and Prevention of the United States identified two cases of human infection with the H1N1 novel influenza virus. The greatest initial burden of critical illness and deaths occurred in Mexico between March and June 2009. The virus is a triple-reassortant containing gene segments from swine influenza virus, human influenza virus, and avian influenza virus. Genes for hemagglutinin and neuraminidase come from swine influenza virus.2 On June 11th, 2009, the World Health Organization raised the level of influenza A (H1N1) pandemic alert from phase 5 to 6, as sustained communitylevel transmission of the virus is taking place in more than one region of the world. Recommendations for the Management of Children With H1N1 Novel Influenza Infection

Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by an RNA virus, influenza A or B virus, of the family Orthomyxoviridae . In humans, common symptoms of influenza infection are fever, sore throat, muscle pains, severe headache, coughing, and weakness and fatigue. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Influenza A viruses are further classified into subtypes based on the antigenic properties of their surface spike glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). There are 18 known HA subtypes (H1-H18) and 10 NA subtypes (N1-N10). HA H17, H18, and NA N10 are divergent species recently isolated from bats. Only H1, H2 and H3 are found in human influenza viruses but virus with H5, H7 and H10 HA have been isolated from humans but without human to human transmission of the viruses. Influenza virus is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds, particularly aquatic birds, through their droppings and contamination of lake water. Influenza spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in non-pandemic years. Three influenza pandemics occurred in the 20th century (1918/9, 1957, and 1968) and to date one in the 21st century (2009). Each of these pandemics was caused by the appearance of a new strain of the virus in humans. These new strains resulted from the direct transfer of an avian virus to humans (1918) or the mixing of genes between human viruses and avian viruses. A highly pathogenic avian virus killed humans in Asia in 1997 and onwards. Up to May 2014 this deadly H5N1 strain has caused 650 cases with 386 fatalities. This virus has posed the greatest risk for a new influenza pandemic. However, this virus has not yet mutated to spread easily among humans. Also, in 2013/14 there have been sporadic isolates of H7N9 and H10N8 from humans in China. Vaccinations against influenza are given to humans. The most common human vaccine is inactivated virus. The vaccine is reformulated each year because influenza virus accumulates point mutations in its surface glycoproteins (antigenic drift) and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors (zanamivir and osteltamivir) being most effective.

Influenza, commonly known as flu, is a contagious, febrile viral disease. Common symptoms are chills, fever, sore throat, coughing, sneezing, muscle pains, headache, myalgia, etc. Influenza viruses (IVs) belonging to orthomyxovirus group are of three types (types A, B, and C). IVs are enveloped, segmented, negative-stranded RNA viruses containing eight distinct RNA segments (types A and B) and seven RNA segments (type C). Only type A viruses exhibit different subtypes. Currently, 18 hemagglutination (HA) subtypes (H1 to H18) and 11 neuraminidase (NA) subtypes (N1 to N11) are known in humans and other warm-blooded animals. Flu outbreaks occur as annual epidemics in fall and winter and infrequently, as worldwide pandemics. Annual epidemics are caused by antigenic drift due to mutations in HA and NA antigens, whereas pandemics are caused by antigenic shift due to genetic reassortment among different subtype viruses. The first pandemic of the twenty-first century, declared by the World Health Organization (WHO) in 2009, was caused by an H1N1 virus, derived from quadruple reassortment among swine, avian, and human IVs. Currently, two types of antiinfluenza drugs, based on either blocking the M2 proton channel (amantadine and rimantadine) or inhibiting NA (oseltamivir or Tamiflu by Roche and zanamivir or Relanza by GlaxoSmithKline) are available. The virus is commonly spread by aerosol droplets and by fingertips. Therefore, washing hands and avoiding contact with infected persons are the first lines of defense. Indoor living and closeness of people in an enclosed environment in winter facilitate virus transmission leading to epidemics. Annual vaccination is the best preventative measure. Currently, two types of vaccines (subunit vaccine by injection and live attenuated vaccine by nasal spray) are available and recommended by WHO and Centers for Disease Control.

Influenza viruses are enveloped viruses with a segmented, single-stranded, negative-sense RNA genome. They attach to host cells via their major surface glycoprotein, hemagglutinin, and are internalized in endocytic compartments. Fusion of the viral membrane with that of the endosome results in the release of the encapsidated viral genome. Viral replication and transcription take place in the nucleus of the infected cell and newly synthesized proteins and viral RNA then assemble at the plasma membrane for packaging into budding virus particles. The ability to manipulate the genome of influenza virus through the advent of reverse genetics has greatly enhanced our understanding of this medically important virus.

Publisher Summary This chapter discusses what is currently known about how individual influenza A virus-encoded proteins and their interactions with host factors contribute to human virulence. It also discusses several functional interactions between influenza A virus proteins, although it has not yet been established whether any or all of these interactions play a role in virulence. Even less is known about the molecular determinants of the virulence of influenza B viruses. One result is probably pertinent—the influenza B virus-encoded nonstructural protein 1 interacts with the cellular IFN system in a novel way that has implications for influenza B virus-induced human diseases. However, the discussion is limited to the molecular determinants of the virulence of influenza A viruses. Influenza A viruses have been reported to induce apoptosis, or programmed cell death, in tissue culture cells. Three influenza A virus-encoded proteins have been ascribed apoptotic functions. NA has been reported to induce apoptosis both directly and indirectly by activating transforming growth factor β, which then functions as the apoptosis inducer. The virulence of influenza A viruses is polygenic. Several virus specific proteins, by their individual actions and/or by their functional interactions with other virus-specific and/or host proteins, likely have important roles in determining how virulent an influenza A virus is in different hosts.

Publisher Summary Human influenza virus was first isolated and identified in the United Kingdom in 1933. The prerequisites for the work on the influenza virus were the discovery of a vital protein of the virus, hemagglutinin (HA); identification of the hemagglutinating ability of the influenza virus in chicken and mammalian erythrocytes; and, most importantly, discovery of the hemagglutination inhibition (HI) test. This chapter focuses on the HA protein of the influenza A virus. The first serological study in animal models and postinfection human sera indicated a surprising degree of antigenic change or drift of the HA. It was the emergence of a completely novel influenza A virus in Asia in 1957 and another in 1968 that confirmed the suspicion—harbored since the Great Spanish Pandemic of 1918—that the influenza A virus had two epidemiological faces or modes, epidemic and pandemic. With the advent of new techniques of protein chemistry and electron microscopy, it has become clear that the HA is the most important antigen of the virus and is made up of two polypeptides—HA1 and HA2. These two constituents of the HA were separated and studied by peptide mapping, and it was discovered that antigenic changes occur entirely in HAl molecules.

Publisher Summary Reverse genetics techniques that allow the genetic manipulation of the influenza virus genome has been developed. It is now possible to engineer transfectant influenza viruses bearing specific mutations into their genomic RNAs. Several molecular strategies have recently been applied to recover transfectant influenza virus vectors expressing novel antigens. The potential use of such vectors as live vaccines against different pathogens and/or diseases is discussed in the chapter. Influenza A viruses comprise different virus subtypes, according to the antigenicity of their external glycoproteins, hemagglutinin (HA), and neuraminidase (NA). The segmented nature of the genome of the virus facilitates the exchange of virus segments between human and avian strains infecting the same cell, resulting in novel human strains. Apart from antigenic shift, influenza A viruses also undergo antigenic drift. This process involves the selection of viruses bearing point mutations in the HA and NA genes that change their antigenic properties. The HA protein is the most important antigenic component of the virus for the induction of a neutralizing antibody response against the virus.

Publisher Summary Influenza is the paradigm of a viral disease in which continued evolution of the virus is of paramount importance for annual epidemics and occasional pandemics of disease in humans. The gene pool of influenza A viruses in aquatic birds provides all the genetic diversity required for the emergence of pandemic influenza viruses for humans, lower animals, and birds. This chapter establishes that rapid evolution in influenza A viruses in humans and other mammals is dependent on periodic introductions of gene segments or entire influenza viruses into humans from the avian influenza virus gene pool. Continuing evolution is most prominent in the surface glycoproteins of influenza viruses but also occurs in each of the eight gene segments of both type A and type B influenza viruses. This variability results from accumulation of molecular changes in the eight RNA segments, which can occur by a number of different mechanisms including: point mutations (antigenic drift), gene reassortment (genetic shift), defective-interfering particles, and RNA recombination. Each of these mechanisms may contribute to the evolution of influenza viruses. Mutations such as substitutions, deletions, and insertions are one of the most important mechanisms for producing variation in influenza viruses. The influenza viruses are unique among the respiratory tract viruses as they undergo significant antigenic variation. Both the surface antigens of the influenza A viruses undergo two types of antigenic variation: antigenic drift and genetic shift.

Publisher Summary This chapter discusses the different aspects of influenza. The highly contagious, acute respiratory illness known as “influenza” appears to have afflicted humans since ancient times. The sudden appearances of respiratory diseases that persist for a few weeks and equally suddenly disappear are sufficiently characteristic to permit the identification of a number of major epidemics in the distant past. Retrospective seroepidemiological analysis, also known as “seroarcheology,” suggests that the influenza epidemic in humans in 1889 and 1890 was caused by a virus antigenically similar to more contemporary Asian strains. The structure of influenza viruses of types A and B is similar, whereas influenza C reveals a different pattern of surface projections. The influenza viruses are unique among the respiratory tract viruses in that they undergo significant antigenic variation. Both of the surface antigens of the influenza A viruses undergo two types of antigenic variation: antigenic drift and antigenic shift. Antigenic drift involves minor antigenic changes in the hemagglutinin (HA) and neuraminidase (NA), whereas shift involves major antigenic changes in these molecules resulting from the replacement of the gene segment.

Publisher Summary This chapter describes cell fusion mediated by influenza virus and discusses genetic approaches to this process. Influenza viruses, with the potential to cause new pandemics or epidemics in an immune population, carry antigenically novel hemagglutinins (HAs). The HA glycoprotein is the major antigen of the influenza virus. It is the ability of these viruses to synthesize antigenically novel HAs that explains the difficulty in controlling the disease. At the same time, the advent of recombinant DNA technology, knowledge of the gene encoding the HA, and X-ray analysis of the structure of the ectodomain of the HA molecule have provided substantial information on its physical domains, the location of antigenic and glycosylation sites, its trimeric structure, and orientation with respect to the plasma membrane. The HA molecule, therefore, constitutes an excellent model system for the study of membrane fusion. Monoclonal antibodies, raised against influenza viruses, have allowed a detailed analysis of the antigenic structure of the protein, and from the studies of the recognition of HA and other viral polypeptides by cytotoxic T-lymphocytes is emerging a complex picture of the cellular immune response to influenza virus. Recently, assays have been developed to monitor the state of folding and oligomerization of nascent and mature forms of HA.

Publisher Summary This chapter discusses cell's role in controlling virus populations that has led to the use of cultured cells to investigate host effects on virus structure, function, and synthesis. Mice and hamsters were also used for early isolations of influenza virus from human sources but in these hosts, unapparent infections occurred following the initial inoculation. The isolation and growth of influenza viruses in embryonated chicken eggs, first reported only two years after the initial isolation of an influenza virus from a human source, revolutionized influenza virus research. The growth of the influenza viruses in chick embryos also made it possible for earlier investigators to identify another kind of genetic variability, which enables host cells to impose selective pressures on influenza virus populations. The first successful attempts at growing the influenza viruses in cultured tissues of chick embryos were reported shortly after the first isolation of human influenza viruses in ferrets. The use of plaque morphology to identify viral strains or to select viral mutants has in general not been of great value for the study of influenza viruses.

In 1977 influenza A(H1N1) virus reappeared into a unique environment; influenza A(H3N2) strains were continuing to circulate, and the majority of the population over the age of 25 years possessed naturally acquired immunity to virus with antigens of H1N1 subtype. The evolution of the virus in this environment has been followed by antigenic

Publisher Summary This chapter provides an overview of Orthomyxoviridae (Genus: Influenza Virus A, influenza virus B, and influenza virus C). In general, the influenza viruses are spherical, enveloped particles with two types of surface glycoprotein spikes and with a genome in the form of eight segments of single-stranded RNA. They infect epithelial cells of the nose, pharynx, trachea and bronchi, and damage to the respiratory epithelium results in the familiar symptoms of influenza disease. Influenza A virus is the classic pandemic virus infection of humans, affecting persons in all areas of the world. Influenza B viruses cause more limited epidemics, whilst influenza C virus is even more benign clinically, although many persons have antibody, suggesting widespread infection. Influenza A virus has an extended host range that includes horses, pigs and aquatic mammals such as seals and whales and also birds, which are infected in the gut. Influenza C virus can also infect pigs but the host range of influenza B virus appears to be restricted to humans. Several genes control the virulence of influenza A viruses, and gene 4 coding for haemagglutinin is considered to be the most important.

Publisher Summary This chapter discusses about the structure of the influenza virion and the various gene products. It focuses on the temperature-sensitive mutants and on the structure of the RNA segments in terms of base sequence, variable and constant genes, and regions within genes, which explain the antigenic variability of the various influenza strains. Influenza viruses are divided into types A, B, and C according to serological differences of their nucleocapsid proteins, which are regarded as group-specific antigens. Evidence in favor of a segmented genome came from observations on multiplicity reactivation and on stepwise inactivation of influenza virus RNA by specific chemicals. For the final assignment of each RNA segment to a corresponding gene function and viral protein, three independent methods are developed. One of these methods takes advantage of the observation that the migration rates of the RNA segments and of the proteins in polyacrylamide gels of various influenza strains are different.

Publisher Summary This chapter discusses the antigenic structure of poliovirus with the focus on the location and nature of the antigenic sites. The structures of two different strains of poliovirus are determined, the Mahoney (neurovirulent) strain of type 1 and the Sabin (attenuated vaccine) strain of type 3 polio virus. Although the structures of the two strains differ in detail, overall the two structures are very similar. The molecular structures of the three large capsid proteins are generally similar to one another. Each is comprised of a conserved core; an eight-stranded antiparallel β-barrel with flanking helices. Where it is relevant, the results with poliovirus are compared in the chapter with those of rhino virus 14 and the influenza antigens to identify general properties that these antigenic sites have in common, and which may be the properties of other viral antigens as well. Moreover, the three-dimensional distribution of antigenic sites is discussed, insofar as it is relevant to understanding the mechanisms of viral escape from neutralization.

Publisher Summary This chapter summarizes recent information on the structure of the hemagglutinin (HA) and neuraminidase (NA), the way in which these glycoproteins vary, and the effects of the changes on the antigenic properties of the virus. Sequences and structures of the two surface glycoprotein antigens of influenza virus provide important information and insight into the mechanism of antigenic variation of influenza virus. Many epitopes exist over most if not all of the accessible surfaces of the HA and NA. These epitopes are critically dependent on the three-dimensional structure of the protein; no effective neutralizing antibodies have been raised when fragments of the protein have been used as immunogens, and neutralizing monoclonal antibodies made against active protein fail to recognize protein that has been denatured by procedures such as drying or methanol fixing on an ELISA plate. A single amino acid change is sufficient to completely destroy binding of a monoclonal antibody to the HA or NA. In natural drift, more than one change is usually found between antigenically distinct isolates, but not as many as there are antigenic sites. It has been demonstrated that attached carbohydrate can mask antigenic determinants, but other factors, as yet undefined, also affect induction of antibodies.

Publisher Summary Particles of influenza virus consist of at least three internal proteins (ribonucleoprotein, matrix protein and RNA-polymerase) contained within a lipid envelope, from which two distinct surface glycoprotein subunits, the hemagglutinin and neuraminidase, protrude as “spikes.” The genome of influenza viruses is segmented, single-stranded RNA which exists in 6 or 7 pieces. RNA isolated from the virus particles is not infectious, probably because it needs to be first transcribed by the virion polymerase into complementary messenger RNA. The segmented nature of the genome allows recombinant viruses (anti-genic hybrids) to be formed readily during mixed infections, and evidence has been obtained which suggests that the viruses responsible for the great human pandemics may be formed by genetic recombination between animal (or avian) influenza viruses and human strains. Such recombinants, having the hemagglutinin or neuraminidase subunits of the animal or avian virus, and the virulence for and the capacity to spread in man, would meet with little antibody resistance in the human population and pandemic influenza would result. Antigenic drift that occurs in influenza viruses between pandemics seems to result from the gradual changes in the amino acid sequence of the polypeptides of the hemagglutinin and neuraminidase subunits.