scholarly journals Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters

2018 ◽  
Author(s):  
Colm Atkins ◽  
Jinxin Miao ◽  
Birte Kalveram ◽  
Terry Juelich ◽  
Jennifer K Smith ◽  
...  
Keyword(s):  
Natural History ◽  
Virus Infection ◽  
Marburg Virus ◽  
Wild Type

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

scholarly journals Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 793
Author(s):  
Ying Huang ◽  
Monique S. França ◽  
James D. Allen ◽  
Hua Shi ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Wild Type ◽  
Influenza A H1n1

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

The Natural History of Hepatitis C Virus Infection in Hemophiliacs

Hematology ◽  
2001 ◽  
Vol 6 (2) ◽  
pp. 135-142 ◽  
Author(s):  
M. Franchini ◽  
A. Tagliaferri ◽  
G. Rossetti ◽  
F. Capra ◽  
E. De Maria ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Natural History ◽  
Virus Infection ◽  
Hepatitis C Virus Infection ◽  
History Of

scholarly journals Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System

2016 ◽  
Vol 68 (10) ◽  
pp. 1014-1020 ◽  
Author(s):  
Martha Grogan ◽  
Christopher G. Scott ◽  
Robert A. Kyle ◽  
Steven R. Zeldenrust ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Natural History ◽  
Risk Stratification ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Wild Type ◽  
History Of

scholarly journals Simian Immunodeficiency Virus Promoter Exchange Results in a Highly Attenuated Strain That Protects against Uncloned Challenge Virus

2004 ◽  
Vol 78 (3) ◽  
pp. 1080-1092 ◽  
Author(s):  
Philippe Blancou ◽  
Nicole Chenciner ◽  
Raphaël Ho Tsong Fang ◽  
Valérie Monceaux ◽  
Marie-Christine Cumont ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Parental Virus ◽  
Wild Type ◽  
Activation Markers ◽  
Challenge Virus ◽  
Immunodeficiency Virus

ABSTRACT Among the many simian immunodeficiency virus (SIV) immunogens, only live attenuated viral vaccines have afforded strong protection to a natural pathogenic isolate. Since the promoter is crucial to the tempo of viral replication in general, it was reasoned that promoter exchange might confer a novel means of attenuating SIV. The core enhancer and promoter sequences of the SIV macaque 239nefstop strain (NF-κB/Sp1 region from −114 bp to mRNA start) have been exchanged for those of the human cytomegalovirus immediate-early promoter (CMV-IE; from −525 bp to mRNA start). During culture of the resulting virus, referred to as SIVmegalo, on CEMx174 or rhesus macaque peripheral blood mononuclear cells, deletions arose in distal regions of the CMV-IE sequences that stabilized after 1 or 2 months of culture. However, when the undeleted form of SIVmegalo was inoculated into rhesus macaques, animals showed highly controlled viremia during primary and persistent infection. Compared to parental virus infection in macaques, primary viremia was reduced by >1,000-fold to undetectable levels, with little sign of an increase of cycling cells in lymph nodes, CD4+ depletion, or altered T-cell activation markers in peripheral blood. Moreover, in contrast to wild-type infection in most infected animals, the nef stop mutation did not revert to the wild-type codon, indicating yet again that replication was dramatically curtailed. Despite such drastic attenuation, antibody titers and enzyme-linked immunospot reactivity to SIV peptides, although slower to appear, were comparable to those seen in a parental virus infection. When animals were challenged intravenously at 4 or 6 months with the uncloned pathogenic SIVmac251 strain, viremia was curtailed by ∼1,000-fold at peak height without any sign of hyperactivation in CD4+- or CD8+-T-cell compartment or increase in lymph node cell cycling. To date, there has been a general inverse correlation between attenuation and protection; however, these findings show that promoter exchange constitutes a novel means to highly attenuate SIV while retaining the capacity to protect against challenge virus.

scholarly journals Conserved Motifs within Ebola and Marburg Virus VP40 Proteins Are Important for Stability, Localization, and Subsequent Budding of Virus-Like Particles

2009 ◽  
Vol 84 (5) ◽  
pp. 2294-2303 ◽  
Author(s):  
Yuliang Liu ◽  
Luis Cocka ◽  
Atsushi Okumura ◽  
Yong-An Zhang ◽  
J. Oriol Sunyer ◽  
...  
Keyword(s):  
Self Assembly ◽  
Mammalian Cells ◽  
Ebola Virus ◽  
Intracellular Localization ◽  
Gel Filtration ◽  
Point Mutations ◽  
Marburg Virus ◽  
Structure Stability ◽  
Wild Type ◽  
Virus Like Particles

ABSTRACT The filovirus VP40 protein is capable of budding from mammalian cells in the form of virus-like particles (VLPs) that are morphologically indistinguishable from infectious virions. Ebola virus VP40 (eVP40) contains well-characterized overlapping L domains, which play a key role in mediating efficient virus egress. L domains represent only one component required for efficient budding and, therefore, there is a need to identify and characterize additional domains important for VP40 function. We demonstrate here that the 96LPLGVA101 sequence of eVP40 and the corresponding 84LPLGIM89 sequence of Marburg virus VP40 (mVP40) are critical for efficient release of VP40 VLPs. Indeed, deletion of these motifs essentially abolished the ability of eVP40 and mVP40 to bud as VLPs. To address the mechanism by which the 96LPLGVA101 motif of eVP40 contributes to egress, a series of point mutations were introduced into this motif. These mutants were then compared to the eVP40 wild type in a VLP budding assay to assess budding competency. Confocal microscopy and gel filtration analyses were performed to assess their pattern of intracellular localization and ability to oligomerize, respectively. Our results show that mutations disrupting the 96LPLGVA101 motif resulted in both altered patterns of intracellular localization and self-assembly compared to wild-type controls. Interestingly, coexpression of either Ebola virus GP-WT or mVP40-WT with eVP40-ΔLPLGVA failed to rescue the budding defective eVP40-ΔLPLGVA mutant into VLPs; however, coexpression of eVP40-WT with mVP40-ΔLPLGIM successfully rescued budding of mVP40-ΔLPLGIM into VLPs at mVP40-WT levels. In sum, our findings implicate the LPLGVA and LPLGIM motifs of eVP40 and mVP40, respectively, as being important for VP40 structure/stability and budding.

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