Interplay of Electron-Phonon Interaction and Electron Correlation in High Temperature Superconductivity

We study the electron-phonon interaction in the strongly correlated superconducting cuprates. Two types of the electron-phonon interactions are introduced in the $t-J$ model; the diagonal and off-diagonal interactions which modify the formation energy of the Zhang-Rice singlet and its transfer integral, respectively. The characteristic phonon-momentum $(\vec q)$ and electron-momentum $(\vec k)$ dependence resulted from the off-diagonal coupling can explain a variety of experiments. The vertex correction for the electron-phonon interaction is formulated in the SU(2) slave-boson theory by taking into account the collective modes in the superconducting ground states. It is shown that the vertex correction enhances the attractive potential for the d-wave paring mediated by phonon with $\vec q=(\pi(1-\delta), 0)$ around $\delta \cong 0.3$ which corresponds to the half-breathing mode of the oxygen motion.Comment: 14 pages, 13 figure

Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility

Chikungunya virus (CHIKV) is a reemerged arbovirus, a member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In the past years, several outbreaks mainly caused by enhanced adaptation of the virus to the vector and ineffective control of the contacts between infected mosquito populations and the human host have been reported. Vaccines represent the best solution for the control of insect-borne viruses, including CHIKV, but are often unavailable. We designed live attenuated CHIKVs by applying a rational genomic design based on multiple replacements of synonymous codons. In doing so, the virus mutational robustness (capacity to maintain phenotype despite introduction of mutations to genotype) is decreased, driving the viral population toward deleterious evolutionary trajectories. When the candidate viruses were tested in the insect and mammalian hosts, we observed overall strong attenuation in both and greatly diminished signs of disease. Moreover, we found that the vaccine candidates elicited protective immunity related to the production of neutralizing antibodies after a single dose. During an experimental transmission cycle between mosquitoes and naive mice, vaccine candidates could be transmitted by mosquito bite, leading to asymptomatic infection in mice with compromised dissemination. Using deep-sequencing technology, we observed an increase in detrimental (stop) codons, which confirmed the effectiveness of this genomic design. Because the approach involves hundreds of synonymous modifications to the genome, the reversion risk is significantly reduced, rendering the viruses promising vaccine candidates

Impact of Extrinsic Incubation Temperature on Natural Selection During Zika Virus Infection of Aedes Aegypti and Aedes Albopictus

Arthropod-borne viruses (arboviruses) require replication across a wide range of temperatures to perpetuate. While vertebrate hosts tend to maintain temperatures of approximately 37°C-40°C, arthropods are subject to ambient temperatures which can have a daily fluctuation of \u3e 10°C. Temperatures impact vector competence, extrinsic incubation period, and mosquito survival unimodally, with optimal conditions occurring at some intermediate temperature. In addition, the mean and range of daily temperature fluctuations influence arbovirus perpetuation and vector competence. The impact of temperature on arbovirus genetic diversity during systemic mosquito infection, however, is poorly understood. Therefore, we determined how constant extrinsic incubation temperatures of 25°C, 28°C, 32°C, and 35°C control Zika virus (ZIKV) vector competence and population dynamics within Aedes aegypti and Aedes albopictus mosquitoes. We also examined fluctuating temperatures which better mimic field conditions in the tropics. We found that vector competence varied in a unimodal manner for constant temperatures peaking between 28°C and 32°C for both Aedes species. Transmission peaked at 10 days post-infection for Aedes aegypti and 14 days for Aedes albopictus. Conversely, fluctuating temperature decreased vector competence. Using RNA-seq to characterize ZIKV population structure, we identified that temperature alters the selective environment in unexpected ways. During mosquito infection, constant temperatures more often elicited positive selection whereas fluctuating temperatures led to strong purifying selection in both Aedes species. These findings demonstrate that temperature has multiple impacts on ZIKV biology, including major effects on the selective environment within mosquitoes

Genome Number and Size Polymorphism in Zika Virus Infectious Units

The arthropod-borne Zika virus (ZIKV) infects humans and can cause severe neurological sequelae, particularly in fetuses infected in utero . How this virus has been able to spread across vast geological ranges and evolve in new host populations is not yet understood. </jats:p

Adventitious viruses persistently infect three commonly used mosquito cell lines

AbstractMosquito cell lines were first established in the 1960’s and have been used extensively in research to isolate and propagate arthropod-borne (arbo-) viruses, study the invertebrate immune system, and understand virus-vector interactions. Despite their utility as anin vitrotool, these cell lines are poorly defined and may harbor insect-specific viruses that could impact experimental results. Accordingly, we screened four commonly-used mosquito cell lines, C6/36 and U4.4 cells fromAedes albopictus, Aag2 cells fromAedes aegypti, and Hsu cells fromCulex quinquefasciatus, for the presence of adventitious viruses. All four cell lines stained positive for double-stranded RNA by immunofluorescence, indicative of RNA virus replication. We subsequently identified viruses infecting Aag2, U4.4 and Hsu cell lines using untargeted next-generation sequencing, but not C6/36 cells. Sequences from viruses in the familiesBirnaviridae,Bunyaviridae, Flaviviridae,andRhabdoviridaewere abundant in the mosquito cell lines. PCR confirmation revealed that these sequences stem from active viral replication and/or integration into the cellular genome. Our results show that these commonly-used mosquito cell lines are persistently-infected with several viruses. This finding may be critical to interpreting data generated in these systems.</jats:p

Virology

Mosquito cell lines have been used extensively in research to isolate and propagate arthropod-borne viruses and understand virus-vector interactions. Despite their utility as an in vitro tool, these cell lines are poorly defined and may harbor insect-specific viruses. Accordingly, we screened four commonly-used mosquito cell lines, C6/36 and U4.4 cells from Aedes albopictus, Aag2 cells from Aedes aegypti, and Hsu cells from Culex quinquefasciatus, for the presence of adventitious (i.e. exogenous) viruses. All four cell lines stained positive for double-stranded RNA, indicative of RNA virus replication. We subsequently identified viruses infecting Aag2, U4.4 and Hsu cell lines using untargeted next-generation sequencing, but not C6/36 cells. PCR confirmation revealed that these sequences stem from active viral replication and/or integration into the cellular genome. Our results show that these commonly-used mosquito cell lines are persistently-infected with several viruses. This finding may be critical to interpreting data generated in these systems.Centers for Disease Control and Prevention [U50/CCU116806-01, U01/CK000509-01]; US Department of Agriculture Hatch Funds and Multistate Research Project [CONH00773, NE1443]; National Institute of Health, National Institute of Allergy and Infectious Diseases [AI067380, AI099042]; NIH/NCATS [UL1 TR001082]This work was supported in part by grants from the Centers for Disease Control and Prevention (U50/CCU116806-01 and U01/CK000509-01), the US Department of Agriculture Hatch Funds and Multistate Research Project (CONH00773 and NE1443), and the National Institute of Health, National Institute of Allergy and Infectious Diseases (AI067380, AI099042), and NIH/NCATS (UL1 TR001082)

Naturally occurring mutations in envelope mediate virulence of Usutu virus

ABSTRACT Usutu virus (USUV) is a mosquito-transmitted flavivirus that is closely related to West Nile virus. Recently, USUV emerged in Europe, where it has caused multiple bird die-off events and neuroinvasive disease in humans. Previously, we showed that USUV isolates from Africa cause significantly more severe disease than European isolates in mice. Sequence analysis revealed that the most virulent isolate (Uganda 2012) and the least virulent isolate (Netherlands 2016) differed by 21 amino acids across the viral polyprotein. Here, we sought to identify the viral determinants of and mechanisms for differential virulence. To accomplish this, we used our USUV reverse genetics system and bacteria-free cloning to generate chimeric viruses between Uganda 2012 and Netherlands 2016. Ifnar1−/− mice infected with a Netherlands 2016 chimera containing all of the structural genes, or just the envelope gene, from Uganda 2012 had significantly higher mortality rates and viremia than those infected with wild-type Netherlands 2016. We were unable to identify a single amino acid in the envelope protein that resulted in significantly increased virulence compared to wild-type Netherlands 2016. These results indicate that multiple mutations in USUV envelope protein contribute to differential virulence between isolates. Through in vitro assays, we discovered that envelope mediates replication kinetics, with fusion occurring more slowly for wild-type Netherlands 2016 compared to viruses containing the envelope from Uganda 2012, suggesting a mechanism for envelope-mediated differential virulence of USUV. These studies provide insights into USUV pathogenic mechanisms, which could be used to evaluate the disease potential of related emerging viruses.IMPORTANCEUsutu virus (USUV) is currently emerging in Europe, where it has caused numerous mass bird die-off events and neuroinvasive disease in humans. Multiple strains of USUV are circulating throughout Europe, but only some of them have been associated with severe disease in humans. The USUV proteins responsible for and the mechanisms through which they cause severe disease are unknown; however, this information could be invaluable in evaluating disease potential of specific strains and the creation of anti-viral therapies. Here, we swapped genes between USUV strains that cause mild and severe disease and were able to identify a viral protein that mediates virulence. We also discovered that the mild strain of USUV takes significantly longer to complete fusion during viral entry into host cells than the severe strain. This delayed fusion could have impacts on cellular tropism, viral kinetics, susceptibility of the virus to immune responses, and, ultimately, disease severity