scholarly journals Quantitative serology assays for determination of antibody responses to Ebola virus glycoprotein and matrix protein in nonhuman primates and humans

2016 ◽  
Vol 126 ◽  
pp. 55-61 ◽  
Author(s):  
Hong Vu ◽  
Sergey Shulenin ◽  
Allen Grolla ◽  
Jonathan Audet ◽  
Shihua He ◽  
...  
2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea Marzi ◽  
Aisling A. Murphy ◽  
Friederike Feldmann ◽  
Christopher J. Parkins ◽  
Elaine Haddock ◽  
...  

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3797-3808 ◽  
Author(s):  
Josh D. Silvertown ◽  
Jagdeep S. Walia ◽  
Alastair J. Summerlee ◽  
Jeffrey A. Medin

The peptide hormone relaxin is a known modulator of connective tissue and the extracellular matrix by virtue of its ability to regulate matrix metalloproteinases (MMPs). Relaxin knockout mice exhibit age-related pulmonary fibrosis, and delivery of recombinant human H2 relaxin ameliorates fibrotic-like conditions in the mouse lung. We investigated whether lentiviral vectors (LVs) engineering the expression of murine relaxins could induce MMP activity in the mouse lung. Mouse relaxin and mouse relaxin-3 peptides engineered by recombinant LVs were biologically active as shown by stimulation of cAMP from both THP-1 and 293T cells stably expressing relaxin receptor LGR7 and by up-regulation of MMP-2 activity from primary C57BL/6 lung cell cultures. To provide the virions with enhanced tropism for the lung, LVs were pseudotyped with the Zaire strain of the Ebola virus glycoprotein (EboZ GP) and delivered by endotracheal intubation. LVs engineering luciferase pseudotyped with EboZ GP, but not with vesicular stomatitis virus glycoprotein resulted in successful LV transduction and transgene expression in C57BL/6 mouse lung by as early as d 4. Mice treated via tracheal delivery with EboZ GP pseudotyped LVs that engineered expression of mouse relaxins exhibited increased MMP-2 and MMP-9 activity in lung tissue up until the end of our study at d 21. Taken together, this study provides proof-of- principle that relaxin gene expression targeted to the mouse lungs can result in enhanced MMP activity offering potential for alleviating disease conditions characterized by dysregulation of extracellular matrix protein accumulation.


2001 ◽  
Vol 125 (5) ◽  
pp. 625-630
Author(s):  
Keith Steele ◽  
Bruce Crise ◽  
Ana Kuehne ◽  
Wayne Kell

Abstract Background.—In vitro studies have previously shown that Ebola virus glycoprotein (GP) is rapidly processed and largely released from infected cells, whereas other viral proteins, such as VP40, accumulate within cells. Objective.—To determine infected cell types in which Ebola virus GP and VP40, individually, localize in vivo. Methods.—Immunohistochemistry and in situ hybridization using GP- and VP40-specific antibodies and genetic probes were used to analyze archived tissues of experimentally infected nonhuman primates and guinea pigs and Vero E6 and 293 cells infected in vitro. Results.—The GP antigen was consistently present in hepatocytes, adrenal cortical cells, fibroblasts, fibroblastic reticular cells, ovarian thecal cells, and several types of epithelial cells, but was not detected in macrophages and blood monocytes of animals, nor in Vero cells and 293 cells. All GP-positive and GP-negative cell types analyzed contained VP40 antigen and both GP and VP40 RNAs. Conclusions.—Ebola virus GP appears to selectively accumulate in many cell types infected in vivo, but not in macrophages and monocytes. This finding suggests that many cell types may have a GP-processing pathway that differs from the pathway described by previous in vitro studies. Differential cellular localization of GP could be relevant to the pathogenesis of Ebola hemorrhagic fever.


2007 ◽  
Vol 81 (6) ◽  
pp. 2995-2998 ◽  
Author(s):  
Gabriele Neumann ◽  
Thomas W. Geisbert ◽  
Hideki Ebihara ◽  
Joan B. Geisbert ◽  
Kathleen M. Daddario-DiCaprio ◽  
...  

ABSTRACT Enveloped viruses often require cleavage of a surface glycoprotein by a cellular endoprotease such as furin for infectivity and virulence. Previously, we showed that Ebola virus glycoprotein does not require the furin cleavage motif for virus replication in cell culture. Here, we show that there are no appreciable differences in disease progression, hematology, serum biochemistry, virus titers, or lethality in nonhuman primates infected with an Ebola virus lacking the furin recognition sequence compared to those infected with wild-type virus. We conclude that glycoprotein cleavage by subtilisin-like endoproteases is not critical for Ebola virus infectivity and virulence in nonhuman primates.


2004 ◽  
Vol 78 (14) ◽  
pp. 7344-7351 ◽  
Author(s):  
Jillian M. Licata ◽  
Reed F. Johnson ◽  
Ziying Han ◽  
Ronald N. Harty

ABSTRACT The VP40 matrix protein of Ebola virus buds from cells in the form of virus-like particles (VLPs) and plays a central role in virus assembly and budding. In this study, we utilized a functional budding assay and cotransfection experiments to examine the contributions of the glycoprotein (GP), nucleoprotein (NP), and VP24 of Ebola virus in facilitating release of VP40 VLPs. We demonstrate that VP24 alone does not affect VP40 VLP release, whereas NP and GP enhance release of VP40 VLPs, individually and to a greater degree in concert. We demonstrate further the following: (i) VP40 L domains are not required for GP-mediated enhancement of budding; (ii) the membrane-bound form of GP is necessary for enhancement of VP40 VLP release; (iii) NP appears to physically interact with VP40 as judged by detection of NP in VP40-containing VLPs; and (iv) the C-terminal 50 amino acids of NP may be important for interacting with and enhancing release of VP40 VLPs. These findings provide a more complete understanding of the role of VP40 and additional Ebola virus proteins during budding.


Author(s):  
Vladimir G. Dedkov ◽  
N’Faly Magassouba ◽  
Olga A. Stukolova ◽  
Victoria A. Savina ◽  
Jakob Camara ◽  
...  

Acute febrile illnesses occur frequently in Guinea. Acute fever itself is not a unique, hallmark indication (pathognomonic sign) of any one illness or disease. In the infectious disease context, fever’s underlying cause can be a wide range of viral or bacterial pathogens, including the Ebola virus. In this study, molecular and serological methods were used to analyze samples from patients hospitalized with acute febrile illness in various regions of Guinea. This analysis was undertaken with the goal of accomplishing differential diagnosis (determination of causative pathogen) in such cases. As a result, a number of pathogens, both viral and bacterial, were identified in Guinea as causative agents behind acute febrile illness. In approximately 60% of the studied samples, however, a definitive determination could not be made.


PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0152527 ◽  
Author(s):  
Jinwoo Lee ◽  
Sonia M. Gregory ◽  
Elizabeth A. Nelson ◽  
Judith M. White ◽  
Lukas K. Tamm

2019 ◽  
Vol 14 (1) ◽  
pp. 21-30
Author(s):  
Janine Brandt ◽  
Lisa Wendt ◽  
Thomas Hoenen

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
Author(s):  
Spencer W. Stonier ◽  
Andrew S. Herbert ◽  
Ana I. Kuehne ◽  
Ariel Sobarzo ◽  
Polina Habibulin ◽  
...  

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.


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