Influenza: old and new threats

Palese, Peter

doi:10.1038/nm1141

Cited by 537 publications

(478 citation statements)

References 37 publications

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“…Influenza provides a particularly interesting historical example (Table 6). Through 80 y of superb research on influenza viruses, we have learned much about the pathogenicity of these viruses in cells in vitro, in animal models in vivo, and in humans in natura, as well as the epidemiological course of seasonal and pandemic infections (124)(125)(126). However, we still know little about the determinism of life-threatening influenza, which occurs in only a minority of infected individuals in the course of epidemic or pandemic influenza (127).…”

Section: Influenza As Another Genetic Diseasementioning

confidence: 99%

“…Moreover, the patient's fibroblasts and iPSC-derived pulmonary epithelial cells also produced only small amounts of the various types of IFN, resulting in enhanced viral replication. This study raises multiple questions, including the proportion of genetic cases among children with severe influenza and the nature of the cells responsible for influenza in patients with IRF7 deficiency (126). We currently are testing the hypothesis that other children with severe influenza carry mutations impairing antiviral immunity.…”

Section: Influenza As Another Genetic Diseasementioning

confidence: 99%

“…There are profound differences between immunity in natural conditions and immunity in experimental conditions, in terms of the pathogen, the route and dose of infection, the host, and the manifestations of infection (130)(131)(132). Influenza in a child living in a small French town (128) has little in common with the injection of influenza virus (which is not rodent-tropic) into an inbred B6 mouse lacking functional myxovirus resistance 1 (Mx1), the key gene product conferring resistance to orthomyxoviruses in rodents (126). The real surprise is the robustness of the infectious phenotypes in mice.…”

Section: Immunological Implicationsmentioning

confidence: 99%

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Severe infectious diseases of childhood as monogenic inborn errors of immunity

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

201

163

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This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

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Section: Influenza As Another Genetic Diseasementioning

confidence: 99%

Section: Influenza As Another Genetic Diseasementioning

confidence: 99%

Section: Immunological Implicationsmentioning

confidence: 99%

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Severe infectious diseases of childhood as monogenic inborn errors of immunity

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

201

163

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“…Seasonal influenza virus infections can produce high morbidity and the emerging threat of pandemic influenza, particularly from an avian source, has become a new concern to the health of the worldwide human population [1][2][3]. The best option for reducing the impact of influenza virus infection in humans is vaccination [4].…”

Section: Introductionmentioning

confidence: 99%

Heterologous HA DNA vaccine prime—inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses

Wang¹,

Parker²,

Taaffe³

et al. 2008

Vaccine

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The trivalent inactivated vaccine (TIV) is used to prevent seasonal influenza virus infection in humans, however, the immunogenicity of this vaccine may be influenced by the priming effect of previous influenza vaccinations or exposure to antigenically-related influenza viruses. The current study examines the immunogenicity of a clinically licensed TIV in rabbits naïve to influenza antigens. Animals were immunized with either the licensed TIV, a bivalent (H1 and H3) HA DNA vaccine or the combination of both. Temporal and peak level serum anti-influenza virus IgG responses were determined by ELISA. Functional antibody responses were measured by hemagglutination inhibition and microneutralization against either A/NewCaledonia//20/99 (H1N1) or A/Panama/2007/99 (H3N2) influenza viruses. Our results demonstrate that the immunogenicity of the TIV is low in seronegative animals. More significantly, the heterologous DNA prime-TIV boost regimen was more immunogenic than the homologous prime-boost using either TIV or DNA vaccines alone. This finding justifies further investigation of HA DNA vaccines as a priming immunogen for the next generation of vaccines against seasonal or pandemic influenza virus infections.

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“…La gripe ha estado presente durante siglos y la relación cercana con ella ha dado lugar a epidemias anuales con patrones estables demográficos y de morbimortalidad 2 . Cada 20-30 años aparece una nueva pandemia, con elevada mortalidad 3,4 . Todas las epidemias importantes de la gripe en seres humanos han sido causadas por los virus de la gripe de origen aviar 3 .…”

Section: Introductionunclassified

Gripe aviar: lo que un intensivista debe conocer

Casillas¹,

Fernandez²,

Varon³

2008

Medicina Intensiva

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En el siglo pasado, la humanidad ha hecho frente a tres de las mayores pandemias de infecciones por el virus de la gripe. La primera fue en 1918, y causó una cantidad significativa de muertes. Éste ha sido también capaz de cruzar la barrera de la especie y afectar a los mamíferos y, lo más preocupante, a los seres humanos. Desde entonces se han publicado varios brotes en el sudeste de Asia. Una gran cantidad de pacientes presenta un curso severo que desarrolla neumonía y disfunción, que implica al hígado, los riñones, el cerebro y los pulmones.Puesto que el virus carece de control regulador de la división genética, experimenta mutaciones constantes que conducen a nuevos subtipos y a nuevas cepas. Los únicos fármacos que han mostrado cierta protección son oseltamivir y zanamivir. Es crucial desarrollar vacunas eficaces y no costosas para prevenir la extensión del virus y la infección, no solamente en seres humanos sino también en aves. PALABRAS CLAVE: gripe aviar, fallo respiratorio agudo, virus H5N1, neuraminidasa, oseltamivir. BIRD FLU: WHAT THE INTENSIVIST MUST KNOWIn the last century, humankind has faced 3 major pandemics of influenza virus infections. The first one occurred in 1918 and caused a significant amount of deaths. It was also capable of crossing over species barrier and affecting mammals, and most worrisome, humans. Since then several outbreaks have been reported in the Southeast of Asia. Many patients with the flu-like illness have a severe course and the patient develops pneumonia and in some cases multiorgan failure involving liver, kidneys, brain and lungs.Since the virus lacks regulatory control of genetic division it undergoes constant mutations leading to new subtypes and, sometimes, new strains. The only drugs that have shown some protection are oseltamivir and zanamivir. It is crucial to develop effective and non-expensive vaccines to prevent the virus spread and infection not only in humans but in birds too.

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Influenza: old and new threats

Cited by 537 publications

References 37 publications

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Heterologous HA DNA vaccine prime—inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses

Gripe aviar: lo que un intensivista debe conocer

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