711 research outputs found
Virology
No full textRift Valley fever virus (RVFV) causes significant morbidity and mortality in humans and livestock throughout Africa and the Middle East. The clinical disease ranges from mild febrile illness, to hepatitis, retinitis, encephalitis and fatal hemorrhagic fever. RVFV NSs protein has previously been shown to interfere in vitro with the interferon response, and RVFV lacking the NSs protein is attenuated in several animal models. Monocytes and macrophages are key players in the innate immune response via expression of various cytokines and chemokines. Here we demonstrate that wild-type RVFV infection of human monocyte-derived macrophages leads to a productive infection and inhibition of the innate immune response via decreased expression of IFN-\u3b12, IFN-\u3b2 and TNF-\u3b1. Using a recombinant virus lacking the NSs protein, we show that this effect is mediated by the viral NSs protein. Finally, analysis of RVF patient samples demonstrated an association between a pro-inflammatory cytokine response and patient survival.CC999999/Intramural CDC HHS/United States2019-04-29T00:00:00Z22018491PMC64874946242vault:3200
NPJ Vaccines
No full textRift Valley fever virus (RVFV) is a zoonotic arbovirus of clinical significance in both livestock and humans. A formalin-inactivated virus preparation was initially developed for human use and tested in laboratory workers in the 1960s. Vaccination resulted in generation of neutralizing antibody titers in most recipients, but neutralization titers waned over time, necessitating frequent booster doses. In this study, T cell-based immune responses to the formalin-inactivated vaccine were examined in a cohort of seven individuals who received between 1 and 6 doses of the vaccine. RVFV-specific T cell responses were detectable up to 24 years post vaccination. Peripheral blood mononuclear cells from this cohort of individuals were used to map out the viral epitopes targeted by T cells in humans. These data provide tools for assessing human RVFV-specific T cell responses and are thus a valuable resource for future human RVFV vaccine efforts.K08 AI119448/AI/NIAID NIH HHS/United States2020-02-28T00:00:00Z32140261PMC7048758821
From star‐forming spirals to passive spheroids: integral field spectroscopy of E+A galaxies
No full textWe present three‐dimensional spectroscopy of 11 E+A galaxies at z = 0.06–0.12. These galaxies were selected for their strong Hδ absorption but weak (or non‐existent) [O ii ] λ3727 and Hα emission. This selection suggests that a recent burst of star formation was triggered but subsequently abruptly ended. We probe the spatial and spectral properties of both the young (≲1 Gyr) and old (≳few Gyr) stellar populations. Using the Hδ equivalent widths we estimate that the burst masses must have been at least 10 per cent by mass ( M burst ≳ 10 10 M ⊙ ), which is also consistent with the star formation history inferred from the broad‐band spectral energy distributions. On average the A stars cover ∼33 per cent of the galaxy image, extending over 2–15 kpc 2 , indicating that the characteristic E+A signature is a property of the galaxy as a whole and not due to a heterogeneous mixture of populations. In approximately half of the sample, we find that the A stars, nebular emission and continuum emission are not co‐located, suggesting that the newest stars are forming in a different place than those that formed ≲1 Gyr ago, and that recent star formation has occurred in regions distinct from the oldest stellar populations. At least 10 of the galaxies (91 per cent) have dynamics that class them as ‘fast rotators’ with magnitudes, v /σ, λ R and bulge‐to‐total (B/T) ratio comparable to local, representative ellipticals and S0s. We also find a correlation between the spatial extent of the A stars and the dynamical state of the galaxy such that the fastest rotators tend to have the most compact A star populations, providing new constraints on models that aim to explain the transformation of later type galaxies into early types. Finally, we show that there are no obvious differences between the line extents and kinematics of E+A galaxies detected in the radio (active galactic nucleus, AGN) compared to non‐radio sources, suggesting that AGN feedback does not play a dramatic role in defining their properties, and/or that its effects are short.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90164/1/j.1365-2966.2011.20082.x.pd
Galaxy Zoo:chiral correlation function of galaxy spins
No full textGalaxy Zoo is the first study of nearby galaxies that contains reliable information about the spiral sense of rotation of galaxy arms for a sizeable number of galaxies. We measure the correlation function of spin chirality (the sense in which galaxies appear to be spinning) of face-on spiral galaxies in angular, real and projected spaces. Our results indicate a hint of positive correlation at separations less than ~0.5 Mpc at a statistical significance of 2-3 sigma. This is the first experimental evidence for chiral correlation of spins. Within tidal torque theory it indicates that the inertia tensors of nearby galaxies are correlated. This is complementary to the studies of nearby spin axis correlations that probe the correlations of the tidal field. Theoretical interpretation is made difficult by the small distances at which the correlations are detected, implying that substructure might play a significant role, and our necessary selection of face-on spiral galaxies, rather than a general volume-limited sample
Virol J
No full textThottapalayam (TPM) virus belongs to the genus Hantavirus, family Bunyaviridae. The genomes of hantaviruses consist of three negative-stranded RNA segments (S, M and L) encoding the virus nucleocapsid (N), glycoprotein (Gn, Gc), and polymerase (L) proteins, respectively. The genus Hantavirus contains predominantly rodent-borne viruses, with the prominent exception of TPM virus which was isolated in India in 1964 from an insectivore, Suncus murinus, commonly referred to as the Asian house shrew or brown musk shrew. Analysis of the available TPM virus S (1530 nt) RNA genome segment sequence and the newly derived M (3621 nt) and L (6581 nt) segment sequences demonstrate that the entire TPM virus genome is very unique. Remarkably high sequence differences are seen at the nucleotide (up to S - 47%, M - 49%, L - 38%) and protein (up to N - 54%, Gn/Gc - 57% and L - 39%) levels relative to the rodent-borne hantaviruses, consistent with TPM virus having a unique host association
Antiviral Res
No full textNipah virus (NiV) outbreaks have occurred in Malaysia, India, and Bangladesh, and the virus continues to cause annual outbreaks of fatal human encephalitis in Bangladesh due to spillover from its bat host reservoir. Due to its high pathogenicity, its potential use for bio/agro-terrorism, and to the current lack of approved therapeutics, NiV is designated as an overlap select agent requiring biosafety level-4 containment. Although the development of therapeutic monoclonal antibodies and soluble protein subunit vaccines have shown great promise, the paucity of effective antiviral drugs against NiV merits further exploration of compound libraries using rapid quantitative antiviral assays. As a proof-of-concept study, we evaluated the use of fluorescent and luminescent reporter NiVs for antiviral screening. We constructed and rescued NiVs expressing either Renilla luciferase or green fluorescent protein, and characterized their reporter signal kinetics in different cell types as well as in the presence of several inhibitors. The 50% effective concentrations (EC50s) derived for inhibitors against both reporter viruses are within range of EC50s derived from virus yield-based dose-response assays against wild-type NiV (within 1Log10), thus demonstrating that both reporter NiVs can serve as robust antiviral screening tools. Utilizing these live NiV-based reporter assays requires modest instrumentation, and circumvents the time and labor-intensive steps associated with cytopathic effect or viral antigen-based assays. These reporter NiVs will not only facilitate antiviral screening, but also the study of host cell components that influence the virus life cycle.CC999999/Intramural CDC HHS/United States2016-11-08T00:00:00Z24680955PMC510074
PLoS Negl Trop Dis
No full textBackgroundRift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood.Methodology/Principal FindingsTo characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (\u394NSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7\u20139 days post-infection. In contrast, inoculation of \u394NSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response.Conclusions/SignificanceComparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) \u394NSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options.20141018
A Case of Ebola virus
No full textDr. Adam MacNeil, an epidemiologist at CDC, discusses Ebola virus.talking with Dr. Adam MacNeil about his case study, Reemerging Sudan Ebola Virus Disease in Uganda, 2011, which appears in the September 2012 issue of CDC\u2019s journal, Emerging Infectious Diseases: Shoemaker, Trevor ; MacNeil, Adam ; Balinandi, Stephen ; Campbell, Shelley ; Wamala, Joseph Francis ; McMullan, Laura K. ; Downing, Robert ; Lutwama, Julius ; Mbidde, Edward ; Str\uf6her, Ute ; Rollin, Pierre E. ; Nichol, Stuart T. Sep 2012. Reemerging Sudan Ebola Virus Disease in Uganda, 2011. Emerg Infect Dis. 18(9):1480-1483.This podcast belongs to the Emerging Infectious Diseases series.Running time = 9:55201
Antiviral Res
No full textCrimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne orthonairovirus, causes a severe hemorrhagic disease in humans (Crimean-Congo hemorrhagic fever, CCHF). Currently, no vaccines are approved to prevent CCHF; treatment is limited to supportive care and the use of ribavirin, the therapeutic benefits of which remain unclear. CCHF is part of WHO's priority list of infectious diseases warranting further research and development. To aid in the identification of new antiviral compounds, we generated a recombinant CCHFV expressing a reporter protein, allowing us to quantify virus inhibition by measuring the reduction in fluorescence in infected cells treated with candidate compounds. The screening assay was readily adaptable to high-throughput screening (HTS) of compounds using Huh7 cells, with a signal-to-noise ratio of 50:1, and Z'-factors\ua0>\ua00.6 in both 96- and 384-well formats. A screen of candidate nucleoside analog compounds identified 2'-deoxy-2'-fluorocytidine (EC|\ua0=\ua061\ua0\ub1\ua018\ua0nM) as having 200\ua0
7\ua0the potency of ribavirin (EC|\ua0=\ua012.5\ua0\ub1\ua02.6\ua0\u3bcM), as well as 17\ua0
7\ua0the potency of T-705 (favipiravir), another compound with reported anti-CCHFV activity (EC|\ua0=\ua01.03\ua0\ub1\ua00.16\ua0\u3bcM). Furthermore, we also determined that 2'-deoxy-2'-fluorocytidine acts synergistically with T-705 to inhibit CCHFV replication without causing cytotoxicity. The incorporation of this reporter virus into the high-throughput screening assay described here will allow more rapid identification of effective therapeutic options to combat this emerging human pathogen.CC999999/ImCDC/Intramural CDC HHSUnited States/R01 AI109008/AI/NIAID NIH HHSUnited States
J Infect Dis
No full textModern ebolavirus diagnostics rely primarily on quantitative reverse transcription-polymerase chain reaction (qRT-PCR), a sensitive method to detect viral genetic material in the acute phase of the disease. However, qRT-PCR does not confirm presence of infectious virus, presenting limitations in patient and outbreak management. Attempts to isolate infectious virus rely on in vivo or basic cell culture approaches, which prohibit rapid results and screening. In this study, we present a novel reporter cell line capable of detecting live ebolaviruses. These cells permit sensitive, large-scale screening and titration of infectious virus in experimental and clinical samples, independent of ebolavirus species and variant.CC999999/Intramural CDC HHSUnited States
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