Counts of Influenza Virus Particles

Donald, Heather B.; Isaacs, A.

doi:10.1099/00221287-10-3-457

Cited by 146 publications

(89 citation statements)

References 10 publications

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“…The present experiments resemble those performed by Liu & Henle (1953) with a mixture of influenza A and B viruses inoculated into the allantoic cavity of the chick embryo, a system to which either hypothesis might conceivably apply since the ID50 dose contains c. 10 virus particles (Donald & Isaacs, 1954). When lo3 ID50 doses or less are inoculated, influenza B grows more slowly than influenza A (Liu & Henle, 1951) so that these viruses can be likened to the Str+ and Str-variants respectively.…”

Section: Discussionmentioning

confidence: 90%

The Applicability of the Hypothesis of Independent Action to Fatal Infections in Mice given Salmonella typhimurium by Mouth

Meynell

1957

Journal of General Microbiology

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SUMMARY:Mice were challenged by mouth with a suspension containing equal numbers of streptomycin-sensitive (Str-) and streptomycin-resistant (Str+) variants of Salmonella typhimurium. These variants were of equal virulence but the Str+ variant grew more slowly in Vivo than the Str-variant. The LD50 dose contained c. 5 x lo6 bacteria. Heart blood obtained from mice dying from many LD50 doses nearly always contained a great excess of the S t r variant, but blood from mice dying from less than one LD 50 dose contained either Str-, Str+, or a mixture of Strand Str+ variants. The appearance of the Str+ variant alone in the latter mice strongly suggests that these fatal infections were initiated by a very small number of organisms or possibly by a single organism. It is therefore concluded that these organisms were acting independently. In this system, it is likely that any bacterium which enters the tissues from the gut can initiate a fatal infection and that the probability of effecting such an entrance almost entirely determines the probability of an inoculated bacterium causing a fatal infection.The inoculation of a partially resistant host with many bacteria will often cause a fatal infection when the inoculation of one bacterium is very unlikely to do so. Of several hypotheses advanced to account for this phenomenon, the most satisfactory appears to be that described elsewhere (Meynell & Stocker, 1957) as the 'hypothesis of independent action' which postulates ( a ) that bacteria act independently after inoculation, and (b) a mean probability (1 > p > 0) per inoculated bacterium of initiating a fatal infection which is constant and unaffected by the number of bacteria inoculated. On this hypothesis therefore, there will always be a chance that the death of a host inoculated with many bacteria will be caused by the progeny of only one of the inoculated bacteria. Although many of the inoculated bacteria may multiply to some extent, the total toxic effect of their clones will never be fatal and will be negligible compared to the toxic effect of the clone descended from only one of the inoculated bacteria. The progenitor of this clone may thus be said to have initiated the fatal infection.A well-known alternative hypothesis is that of the minimal lethal dose which postulates that if the dose exceeds a critical minimum size, death is inevitable; while if it is smaller than the minimum, the host is certain to survive. Thus, a lethal dose might be supposed to saturate the host defences so that death follows the multiplication either of all the inoculated bacteria or of those bacteria not needed for saturation. I n the latter case, a fatal infection could * Present address.

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Section: Discussionmentioning

confidence: 90%

The Applicability of the Hypothesis of Independent Action to Fatal Infections in Mice given Salmonella typhimurium by Mouth

Meynell

1957

Journal of General Microbiology

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“…All tissue-culture virus titers were determined by end-point dilution on MDCK cells, and the TCID 50 was determined using the Reed-Muench method. Physical virus particles were enumerated using turkey RBCs as previously described (37), based on the observation that at hemagglutination end point the number of particles equals the number of erythrocytes. Titers of HA-expressing units (HAEU) and NA-expressing units (NAEU) were determined by infecting cultures of MDCK cells with serial dilutions of virus.…”

Section: Methodsmentioning

confidence: 99%

Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility

Brooke

Ince

Wei

et al. 2014

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

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The influenza A virus (IAV) genome is divided into eight distinct RNA segments believed to be copackaged into virions with nearly perfect efficiency. Here, we describe a mutation in IAV nucleoprotein (NP) that enhances replication and transmission in guinea pigs while selectively reducing neuraminidase (NA) gene segment packaging into virions. We show that incomplete IAV particles lacking gene segments contribute to the propagation of the viral population through multiplicity reactivation under conditions of widespread coinfection, which we demonstrate commonly occurs in the upper respiratory tract of guinea pigs. NP also dramatically altered the functional balance of the viral glycoproteins on particles by selectively decreasing NA expression. Our findings reveal novel functions for NP in selective control of IAV gene packaging and balancing glycoprotein expression and suggest a role for incomplete gene packaging during host adaptation and transmission.influenza virus | genome segmentation | genome packaging | nucleoprotein | host adaptation S easonal influenza A virus (IAV) remains a major public health threat, causing tens of thousands of deaths each year in the United States alone (1). Morbidity and mortality rates can increase dramatically when a zoonotic strain adapts to circulate in humans, triggering a pandemic. The continuing toll exerted by IAV stems from its remarkable adaptability, which enables it to move between widely divergent host species and also evade herd immunity within each species. Defining the specific mechanisms that mediate IAV adaptation is essential to improving anti-IAV vaccines, therapeutics, and pandemic surveillance.The IAV genome consists of eight negative-sense RNA segments, each of which is required for productive infection. Genome segmentation complements the high mutation rate of IAV by facilitating reassortment, which can maximize positive intergenic epistasis (2-5) and allow selective elimination of segments with deleterious mutations (6, 7). Although reassortment is the most obvious and best-characterized benefit of segmentation, there are likely additional evolutionary advantages.Genome segmentation imposes the substantial constraint of maintaining a gene-packaging mechanism to produce fully infectious virions (8). For IAV, it is widely believed that a single copy of each segment is packaged into progeny virions with nearly perfect efficiency, resulting in an equimolar ratio of the segments at the population level (9-12). Confounding this model, we recently demonstrated that most IAV virions fail to express one or more gene products (13). This finding raises the possibility that in some circumstances incomplete influenza gene packaging is evolutionarily neutral and possibly even advantageous (14).The viral glycoproteins HA and neuraminidase (NA) are encoded by separate genome segments. HA attaches IAV to terminal sialic acid residues on the host cell surface, enabling viral entry. By hydrolyzing sialic acids, NA detaches budding virions and neutralizes HA-inhibiting glyco...

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“…measurements (Donald & Isaacs, 1954;Hutchinson et al, 2008;Kingsbury, 1970;Nakajima & Sugiura, 1977). Consequently, it was concluded that there must be some form of segment specificity in genome packaging (Laver & Downie, 1976;Nakajima & Sugiura, 1977).…”

Section: Genome Segmentation: a Mixed Blessingmentioning

confidence: 99%