The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses antiviral restriction factors to defend against infection. To find host cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism, and RNA splicing. We discovered that the interferon-inducible transmembrane proteins IFITM1, 2, and 3 restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus but are also inducible by interferons type I and II and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a family of antiviral restriction factors that mediate cellular innate immunity to at least three major human pathogens.

Wide prevalence of hybridization in two sympatric grasshopper species may be shaped by their relative abundances.

BACKGROUND: Hybridization between species is of conservation concern as it might threaten the genetic integrity of species. Anthropogenic factors can alter hybridization dynamics by introducing new potentially hybridizing species or by diminishing barriers to hybridization. This may even affect sympatric species pairs through environmental change, which so far has received little attention. We studied hybridization prevalence and the underlying behavioral mechanisms in two sympatric grasshopper species, a rare specialist (Chorthippus montanus) and a common generalist (Chorthippus parallelus). We conducted a mate choice experiment with constant intraspecific density and varying heterospecific density, i.e. varying relative frequency of both species. RESULTS: Mate choice was frequency-dependent in both species with a higher risk of cross-mating with increasing heterospecific frequency, while conspecific mating increased linearly with increasing conspecific density. This illustrates that reproductive barriers could be altered by environmental change, if the relative frequency of species pairs is affected. Moreover, we performed a microsatellite analysis to detect hybridization in twelve syntopic populations (and four allotopic populations). Hybrids were detected in nearly all syntopic populations with hybridization rates reaching up to 8.9 %. Genetic diversity increased for both species when hybrids were included in the data set, but only in the common species a positive correlation between hybridization rate and genetic diversity was detected. CONCLUSION: Our study illustrates that the relative frequency of the two species strongly determines the effectiveness of reproductive barriers and that even the more choosy species (Ch. montanus) may face a higher risk of hybridization if population size decreases and its relative frequency becomes low compared to its sister species. The asymmetric mate preferences of both species may lead to quasi-unidirectional gene flow caused by unidirectional backcrossing. This might explain why genetic diversity increased only in the common species, but not in the rare one. Altogether, the hybridization rate was much higher than expected for a widely sympatric species pair.

Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2)) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-ß specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

Permanent genetic resources added to molecular ecology resources database 1 April 2012 - 31 May 2012.

This article documents the addition of 123 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Brenthis ino, Cichla orinocensis, Cichla temensis, Epinephelus striatus, Gobio gobio, Liocarcinus depurator, Macrolophus pygmaeus, Monilinia vaccinii-corymbosi, Pelochelys cantorii, Philotrypesis josephi, Romanogobio vladykovi, Takydromus luyeanus and Takydromus viridipunctatus. These loci were cross-tested on the following species: Cichla intermedia, Cichla ocellaris, Cichla pinima, Epinephelus acanthistius, Gobio carpathicus, Gobio obtusirostris, Gobio sp. 1, Gobio volgensis, Macrolophus costalis, Macrolophus melanotoma, Macrolophus pygmaeus, Romanogobio albipinnatus, Romanogobio banaticus, Romanogobio belingi, Romanogobio kesslerii, Romanogobio parvus, Romanogobio pentatrichus, Romanogobio uranoscopus, Takydromus formosanus, Takydromus hsuehshanesis and Takydromus stejnegeri.