Multinational Impact of the 1968 Hong Kong Influenza Pandemic: Evidence for a Smoldering Pandemic

Viboud, Cécile; Grais, Rebecca F.; Lafont, Bernard A. P.; Miller, Mark A.; Simonsen, Lone

doi:10.1086/431150

Cited by 215 publications

(209 citation statements)

References 34 publications

(51 reference statements)

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“…Previous studies have pointed out the importance of NA-based immunity in curbing the severity or spread of emerging strains with novel HAs. Epidemiologic analyses (25,26) support the concept that NA antibodies contributed to protection against the 1968 pandemic H3N2 virus that possessed an NA antigenically similar to that of the previously circulating H2N2 lineage (27,28). In addition, antibodies directed to conserved regions of NA may contribute a significant level of protection against disease: the presence of such heterologous immunity has been demonstrated in H3N2 (29) and H5N1 (30) challenge studies in mice.…”

Section: Single Amino Acid Change Is Largely Responsible For the Antimentioning

confidence: 78%

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

Sandbulte

Westgeest²,

Gao³

et al. 2011

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

210

185

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Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.

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Section: Single Amino Acid Change Is Largely Responsible For the Antimentioning

confidence: 78%

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

Sandbulte

Westgeest²,

Gao³

et al. 2011

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

210

185

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“…Recent epidemiological studies of pandemic and inter-pandemic influenza suggest that antigenic changes in the haemagglutinin, the most studied component of antibody-mediated immunity, may not be the only determinant of viral fitness and ability to spread in a population [19,21]. The exact relationship between virus antigenic changes and population dynamics is still unclear, and a key area for future research.…”

Section: Discussionmentioning

confidence: 99%

Seasonal influenza in the United States, France, and Australia: transmission and prospects for control

2007

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SUMMARYRecurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia. We found similar distributions of reproduction number estimates in the three countries, with mean value 1.3 and important year-to-year variability (range 0.9-2.1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation = 0.61, P < 0.001) and France (correlation = 0.79, P < 0.001), but not Australia. Interestingly, high prevalence of A/H3N2 influenza viruses was associated with high transmission seasons (P = 0.006), while B viruses were more prevalent in low transmission seasons (P = 0.004). The current vaccination strategy targeted at people at highest risk of severe disease outcome is suboptimal because current vaccines are poorly immunogenic in these population groups. Our results suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (> 60 %) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.

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“…Wild aquatic birds are known to be the natural reservoirs of these subtypes (22,42,54); however, through adaptive evolution and reassortment, virus variants acquire the ability to transmit among avian and mammalian hosts including humans. In the last 100 years four influenza pandemics have occurred by adaptation of animal and avian viruses or genes, resulting in human viruses, as seen in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1) (16,20,27,33,36,37,49).…”

mentioning

confidence: 99%

PB2 and Hemagglutinin Mutations Are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus

Ping

Dankar

Forbes

et al. 2010

J Virol

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Serial mouse lung passage of a human influenza A virus, A/Hong Kong/1/68 (H3N2) (HK-wt), produced a mouse-adapted variant, MA, with nine mutations that was >10 3.8 -fold more virulent. In this study, we demonstrate that MA mutations of the PB2 (D701N) and hemagglutinin (HA) (G218W in HA1 and T156N in HA2) genes were the most adaptive genetic determinants for increased growth and virulence in the mouse model. Recombinant viruses expressing each of the mutated MA genome segments on the HK-wt backbone showed significantly increased disease severity, whereas only the mouse-adapted PB2 gene increased virulence, as determined by the 50% lethal dose ([LD 50 ] >101.4 -fold). The converse comparisons of recombinant MA viruses expressing each of the HK-wt genome segments showed the greatest decrease in virulence due to the HA gene (10 2 -fold), with lesser decreases due to the M1, NS1, NA, and PB1 genes (10 0.3 -to 10 0.8 -fold), and undetectable effects on the LD 50 for the PB2 and NP genes. The HK PB2 gene did, however, attenuate MA infection, as measured by weight loss and time to death. Replication of adaptive mutations in vivo and in vitro showed both viral gene backbone and host range effects. Minigenome transcription assays showed that PB1 and PB2 mutations increased polymerase activity and that the PB2 D701N mutation was comparable in effect to the mammalian adaptive PB2 E627K mutation. Our results demonstrate that host range and virulence are controlled by multiple genes, with major roles for mutations in PB2 and HA.

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Multinational Impact of the 1968 Hong Kong Influenza Pandemic: Evidence for a Smoldering Pandemic

Cited by 215 publications

References 34 publications

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses

Seasonal influenza in the United States, France, and Australia: transmission and prospects for control

PB2 and Hemagglutinin Mutations Are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus

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