Inferring patterns of influenza transmission in swine from multiple streams of surveillance data

Swine populations are known to be an important source of new human strains of influenza A, including those responsible for global pandemics. Yet our knowledge of the epidemiology of influenza in swine is dismayingly poor, as highlighted by the emergence of the 2009 pandemic strain and the paucity of data describing its origins. Here, we analyse a unique dataset arising from surveillance of swine influenza at a Hong Kong abattoir from 1998 to 2010. We introduce a state–space model that estimates disease exposure histories by joint inference from multiple modes of surveillance, integrating both virological and serological data. We find that an observed decrease in virus isolation rates is not due to a reduction in the regional prevalence of influenza. Instead, a more likely explanation is increased infection of swine in production farms, creating greater immunity to disease early in life. Consistent with this, we find that the weekly risk of exposure on farms equals or exceeds the exposure risk during transport to slaughter. We discuss potential causes for these patterns, including competition between influenza strains and shifts in the Chinese pork industry, and suggest opportunities to improve knowledge and reduce prevalence of influenza in the region.     

Avian influenza virus directly infects human natural killer cells and inhibits cell activity

Natural killer (NK) cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously, we showed that human influenza H1N1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza, and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.

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Is Exercise Protective Against Influenza-Associated Mortality?

Background

Little is known about the effect of physical exercise on influenza-associated mortality.

Methods and Findings

We collected information about exercise habits and other lifestyles, and socioeconomic and demographic status, the underlying cause of death of 24,656 adults (21% aged 30–64, 79% aged 65 or above) who died in 1998 in Hong Kong, and the weekly proportion of specimens positive for influenza A (H3N1 and H1N1) and B isolations during the same period. We assessed the excess risks (ER) of influenza-associated mortality due to all-natural causes, cardiovascular diseases, or respiratory disease among different levels of exercise: never/seldom (less than once per month), low/moderate (once per month to three times per week), and frequent (four times or more per week) by Poisson regression. We also assessed the differences in ER between exercise groups by case-only logistic regression. For all the mortality outcomes under study in relation to each 10% increase in weekly proportion of specimens positive for influenza A+B, never/seldom exercise (as reference) was associated with 5.8% to 8.5% excess risks (ER) of mortality (P<0.0001), while low/moderate exercise was associated with ER which were 4.2% to 6.4% lower than those of the reference (P<0.001 for all-natural causes; P = 0.001 for cardiovascular; and P = 0.07 for respiratory mortality). Frequent exercise was not different from the reference (change in ER −0.8% to 1.7%, P = 0.30 to 0.73).

Conclusion

When compared with never or seldom exercise, exercising at low to moderate frequency is beneficial with lower influenza-associated mortality.     

Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

Background

The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection.

Methods and Findings

Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM⁺ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge.

Conclusions

The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM⁺ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens.     

Supervised Lowess normalization of comparative genome hybridization data – application to lactococcal strain comparisons

Background

Visualising the evolutionary history of a set of sequences is a challenge for molecular phylogenetics. One approach is to use undirected graphs, such as median networks, to visualise phylogenies where reticulate relationships such as recombination or homoplasy are displayed as cycles. Median networks contain binary representations of sequences as nodes, with edges connecting those sequences differing at one character; hypothetical ancestral nodes are invoked to generate a connected network which contains all most parsimonious trees. Quasi-median networks are a generalisation of median networks which are not restricted to binary data, although phylogenetic information contained within the multistate positions can be lost during the preprocessing of data. Where the history of a set of samples contain frequent homoplasies or recombination events quasi-median networks will have a complex topology. Graph reduction or pruning methods have been used to reduce network complexity but some of these methods are inapplicable to datasets in which recombination has occurred and others are procedurally complex and/or result in disconnected networks.

Results

We address the problems inherent in construction and reduction of quasi-median networks. We describe a novel method of generating quasi-median networks that uses all characters, both binary and multistate, without imposing an arbitrary ordering of the multistate partitions. We also describe a pruning mechanism which maintains at least one shortest path between observed sequences, displaying the underlying relations between all pairs of sequences while maintaining a connected graph.

Conclusion

Application of this approach to 5S rDNA sequence data from sea beet produced a pruned network within which genetic isolation between populations by distance was evident, demonstrating the value of this approach for exploration of evolutionary relationships.     

Evaluation of the Inheritance of the Complex Vertebral Malformation Syndrome by Breeding Studies

To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses. The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders.     

A newly discovered verotoxin variant, VT2g, produced by bovine verocytotoxigenic Escherichia coli

A new verotoxin (VT) variant, designated vt2g, was identified from a bovine strain of verocytotoxigenic Escherichia coli (VTEC) serotype O2:H25. When vt2g was aligned with published sequences of vt2 and vt variants, it exhibited the highest DNA sequence homology with vt2 and vt2c. However, vt2g was not detected by vt2-specific primers and probes, although it was partially neutralized by an antiserum to the VT2A subunit. VT2g was cytotoxic for Vero and HeLa cells and was not activated by mouse intestinal mucus. The vt2g gene was detected in 3 of 409 (0.7%) bovine VTEC strains, including serotypes O2:H25, O2:H45 and Ont:H-.     

Distribution patterns of coconut mite, Aceria guerreronis, and its predator Neoseiulus aff. paspalivorus in coconut palms

Distribution patterns and numerical variability of the coconut mite Aceria guerreronis Keifer (Acari: Eriophyidae) and its predator Neoseiulus aff. paspalivorus DeLeon (Phytoseiidae) on the nuts of 3- to 7-month-old bunches of coconut palms were studied at two sites in Sri Lanka. At the two sites, coconut mites were present on 88 and 75% of the nuts but no more than three-quarters of those nuts showed damage symptoms. N. aff. paspalivorus was found more on mature nuts than on immature nuts. Spatial and temporal distribution of coconut mites and predatory mites differed significantly. The mean number of coconut mites per nut increased until 5-month-old bunches and declined thereafter. The densities of predatory mites followed a similar trend but peaked 1 month later. Variability in the numbers of mites among palms and bunches of the same age was great, but was relatively low on 6-month-old bunches. The results indicate that assessment of infestation levels by damage symptoms alone is not reliable. Sampling of coconut and/or predatory mite numbers could be improved by using several nuts of 6-month-old bunches. The effect of predatory mites on coconut mites over time suggests that N. aff. paspalivorus could be a prospective biological control agent of A. guerreronis.