Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in Ifnar-/- mice

Welch, Stephen R.; Ritter, Jana M.; McElroy, Anita K.; Harmon, Jessica R.; Coleman-McCray, JoAnn D.; Scholte, Florine M.; Kobinger, Gary P.; Bergeron, Éric; Zaki, Sherif R.; Nichol, Stuart T.; Spengler, Jessica R.; Spiropoulou, Christina F.

doi:10.1371/journal.ppat.1008183

Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in Ifnar^-/- mice

Journal Article · Sun Dec 01 23:00:00 EST 2019 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1008183· OSTI ID:1904893

Welch, Stephen R. ^[1]; Ritter, Jana M. ^[2]; ^[3]; ^[2]; Coleman-McCray, JoAnn D. ^[2]; ^[2]; Kobinger, Gary P. ^[4]; ^[2]; Zaki, Sherif R. ^[2]; Nichol, Stuart T. ^[2]; ^[2]; ^[2]

Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); OSTI
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); University of Pittsburgh, PA (United States)
Universite Laval, Quebec City (Canada)

Crimean-Congo hemorrhagic fever virus (CCHFV, order Bunyavirales, family Nairoviridae, genus Orthonairovirus) is the tick-borne etiological agent of Crimean-Congo hemorrhagic fever (CCHF) in humans. Animals are generally susceptible to CCHFV infection but refractory to disease. Small animal models are limited to interferon-deficient mice, that develop acute fatal disease following infection. Here, using a ZsGreen1- (ZsG) expressing reporter virus (CCHFV/ZsG), we examine tissue tropism and dissemination of virus in interferon-α/β receptor knock-out (Ifnar^-/-) mice. We demonstrate that CCHFV/ZsG retains in vivo pathogenicity comparable to wild-type virus. Interestingly, despite high levels of viral RNA in all organs assessed, 2 distribution patterns of infection were observed by both fluorescence and immunohistochemistry (IHC), corresponding to the permissiveness of organ tissues. To further investigate viral dissemination and to temporally define cellular targets of CCHFV in vivo, mice were serially euthanized at different stages of disease. Flow cytometry was used to characterize CCHFV-associated alterations in hematopoietic cell populations and to classify infected cells in the blood, lymph node, spleen, and liver. ZsG signal indicated that mononuclear phagocytic cells in the lymphatic tissues were early targets of infection; in latestage infection, overall, the highest levels of signal were detected in the liver, and ZsG was found in both antigen-presenting and lymphocyte cell populations.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC); Centers for Disease Control and Prevention

Grant/Contract Number:: SC0014664

OSTI ID:: 1904893

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 12 Vol. 15; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (70)

Crimean-Congo hemorrhagic fever: CXCL10 correlates with the viral load Papa, Anna; Yagci Caglayık, Dilek; Christova, Iva Journal of Medical Virology, Vol. 87, Issue 6 https://doi.org/10.1002/jmv.24141	journal	February 2015
Cytokines as biomarkers of Crimean-Congo hemorrhagic fever Papa, Anna; Tsergouli, Katerina; Çağlayık, Dilek Yağcı Journal of Medical Virology, Vol. 88, Issue 1 https://doi.org/10.1002/jmv.24312	journal	July 2015
Cytokine response in crimean-congo hemorrhagic fever virus infection Ergönül, Önder; Şeref, Ceren; Eren, Şebnem Journal of Medical Virology, Vol. 89, Issue 10 https://doi.org/10.1002/jmv.24864	journal	July 2017
Severe fever with thrombocytopenia syndrome (SFTS) treated with a novel antiviral medication, favipiravir (T-705) Song, Rui; Chen, Zhihai; Li, Wei Infection, Vol. 48, Issue 2 https://doi.org/10.1007/s15010-019-01364-9	journal	October 2019
Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease Perry, Donna L.; Huzella, Louis M.; Bernbaum, John G. The American Journal of Pathology, Vol. 188, Issue 3 https://doi.org/10.1016/j.ajpath.2017.11.004	journal	March 2018
Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity Bente, Dennis A.; Forrester, Naomi L.; Watts, Douglas M. Antiviral Research, Vol. 100, Issue 1 https://doi.org/10.1016/j.antiviral.2013.07.006	journal	October 2013
Identification of 2′-deoxy-2′-fluorocytidine as a potent inhibitor of Crimean-Congo hemorrhagic fever virus replication using a recombinant fluorescent reporter virus Welch, Stephen R.; Scholte, Florine E. M.; Flint, Mike Antiviral Research, Vol. 147 https://doi.org/10.1016/j.antiviral.2017.10.008	journal	November 2017
Heterologous protection against Crimean-Congo hemorrhagic fever in mice after a single dose of replicon particle vaccine Spengler, Jessica R.; Welch, Stephen R.; Scholte, Florine E. M. Antiviral Research, Vol. 170 https://doi.org/10.1016/j.antiviral.2019.104573	journal	October 2019
Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease Scholte, Florine E. M.; Zivcec, Marko; Dzimianski, John V. Cell Reports, Vol. 20, Issue 10 https://doi.org/10.1016/j.celrep.2017.08.040	journal	September 2017
Clinical and laboratory features of Crimean-Congo hemorrhagic fever: predictors of fatality Çevik, Mustafa A.; Erbay, Ayse; Bodur, Hürrem International Journal of Infectious Diseases, Vol. 12, Issue 4 https://doi.org/10.1016/j.ijid.2007.09.010	journal	July 2008
Analysis of lymphocyte subgroups in Crimean-Congo hemorrhagic fever Akıncı, Esragül; Yılmaz, Mesude; Bodur, Hürrem International Journal of Infectious Diseases, Vol. 13, Issue 5 https://doi.org/10.1016/j.ijid.2008.08.027	journal	September 2009
Possible sexual transmission of Crimean-Congo hemorrhagic fever Pshenichnaya, Natalia Yurievna; Sydenko, Irina Stanislavovna; Klinovaya, Elena Pavlovna International Journal of Infectious Diseases, Vol. 45 https://doi.org/10.1016/j.ijid.2016.02.1008	journal	April 2016
Peripheral blood natural killer cells in Crimean-Congo hemorrhagic fever Yilmaz, Mustafa; Aydin, Kemalettin; Akdogan, Elif Journal of Clinical Virology, Vol. 42, Issue 4 https://doi.org/10.1016/j.jcv.2008.03.003	journal	August 2008
Crimean-Congo hemorrhagic fever treated with ribavirin in a pregnant woman Dizbay, Murat; Aktas, Firdevs; Gaygisiz, Ummugulsum Journal of Infection, Vol. 59, Issue 4 https://doi.org/10.1016/j.jinf.2009.08.004	journal	October 2009
Crimean-Congo haemorrhagic fever Ergönül, Önder The Lancet Infectious Diseases, Vol. 6, Issue 4 https://doi.org/10.1016/s1473-3099(06)70435-2	journal	April 2006
Viraemic transmission of Crimean-Congo haemorrhagic fever virus to ticks Shepherd, A. J.; Swanepoel, R.; Shepherd, S. P. Epidemiology and Infection, Vol. 106, Issue 2 https://doi.org/10.1017/s0950268800048524	journal	April 1991
A cynomolgus macaque model for Crimean–Congo haemorrhagic fever Haddock, Elaine; Feldmann, Friederike; Hawman, David W. Nature Microbiology, Vol. 3, Issue 5 https://doi.org/10.1038/s41564-018-0141-7	journal	April 2018
Molecular Evidence of Sexual Transmission of Ebola Virus Mate, Suzanne E.; Kugelman, Jeffrey R.; Nyenswah, Tolbert G. New England Journal of Medicine, Vol. 373, Issue 25 https://doi.org/10.1056/nejmoa1509773	journal	December 2015
Single-dose replicon particle vaccine provides complete protection against Crimean-Congo hemorrhagic fever virus in mice Scholte, Florine E. M.; Spengler, Jessica R.; Welch, Stephen R. Emerging Microbes & Infections, Vol. 8, Issue 1 https://doi.org/10.1080/22221751.2019.1601030	journal	January 2019
Evaluation of Serum Levels of Interleukin (IL)–6, IL‐10, and Tumor Necrosis Factor–α in Patients with Crimean‐Congo Hemorrhagic Fever Ergonul, Onder; Tuncbilek, Semra; Baykam, Nurcan The Journal of Infectious Diseases, Vol. 193, Issue 7 https://doi.org/10.1086/500836	journal	April 2006
Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days Diallo, Boubacar; Sissoko, Daouda; Loman, Nicholas J. Clinical Infectious Diseases, Vol. 63, Issue 10 https://doi.org/10.1093/cid/ciw601	journal	September 2016
The Clinical Pathology of Crimean-Congo Hemorrhagic Fever Swanepoel, R.; Gill, D. E.; Shepherd, A. J. Clinical Infectious Diseases, Vol. 11, Issue Supplement_4 https://doi.org/10.1093/clinids/11.supplement_4.s794	journal	May 1989
New Evidence of Long-lasting Persistence of Ebola Virus Genetic Material in Semen of Survivors: Table 1. Sow, Mamadou S.; Etard, Jean-François; Baize, Sylvain Journal of Infectious Diseases, Vol. 214, Issue 10 https://doi.org/10.1093/infdis/jiw078	journal	May 2016
Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection Spengler, Jessica R.; Kelly Keating, M.; McElroy, Anita K. The Journal of Infectious Diseases, Vol. 216, Issue 11 https://doi.org/10.1093/infdis/jix215	journal	May 2017
A Simple Method of Estimating Fifty per cent Endpoints12 Reed, L. J.; Muench, H. American Journal of Epidemiology, Vol. 27, Issue 3 https://doi.org/10.1093/oxfordjournals.aje.a118408	journal	May 1938
Clinical severity in forecasting platelet to lymphocyte ratio in Crimean–Congo hemorrhagic fever patients Eren, Sevki Hakan; Zengin, Suat; Büyüktuna, Seyit Ali Journal of Medical Microbiology, Vol. 65, Issue 10 https://doi.org/10.1099/jmm.0.000330	journal	October 2016
Differential activation profiles of Crimean-Congo hemorrhagic fever virus- and Dugbe virus-infected antigen-presenting cells Peyrefitte, C. N.; Perret, M.; Garcia, S. Journal of General Virology, Vol. 91, Issue 1 https://doi.org/10.1099/vir.0.015701-0	journal	October 2009
Crimean-Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout mice Bereczky, S.; Lindegren, G.; Karlberg, H. Journal of General Virology, Vol. 91, Issue 6 https://doi.org/10.1099/vir.0.019034-0	journal	February 2010
Pregnancy and Crimean-Congo haemorrhagic fever Ergonul, O.; Celikbas, A.; Yildirim, U. Clinical Microbiology and Infection, Vol. 16, Issue 6 https://doi.org/10.1111/j.1469-0691.2009.02905.x	journal	June 2010
Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever Saksida, A.; Duh, D.; Wraber, B. Clinical and Vaccine Immunology, Vol. 17, Issue 7 https://doi.org/10.1128/cvi.00530-09	journal	May 2010
Crimean-Congo Hemorrhagic Fever Mouse Model Recapitulating Human Convalescence Hawman, David W.; Meade-White, Kimberly; Haddock, Elaine Journal of Virology, Vol. 93, Issue 18 https://doi.org/10.1128/jvi.00554-19	journal	September 2019
Exploring Crimean-Congo Hemorrhagic Fever Virus-Induced Hepatic Injury Using Antibody-Mediated Type I Interferon Blockade in Mice Lindquist, Michael E.; Zeng, Xiankun; Altamura, Louis A. Journal of Virology, Vol. 92, Issue 21 https://doi.org/10.1128/jvi.01083-18	journal	August 2018
Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model Bente, D. A.; Alimonti, J. B.; Shieh, W. -J. Journal of Virology, Vol. 84, Issue 21 https://doi.org/10.1128/jvi.01383-10	journal	August 2010
Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells Connolly-Andersen, A. -M.; Moll, G.; Andersson, C. Journal of Virology, Vol. 85, Issue 15 https://doi.org/10.1128/jvi.02469-10	journal	June 2011
Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry Martinez, O.; Johnson, J. C.; Honko, A. Journal of Virology, Vol. 87, Issue 7 https://doi.org/10.1128/jvi.02695-12	journal	January 2013
In Vivo Imaging of Influenza Virus Infection in Immunized Mice Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W. mBio, Vol. 8, Issue 3 https://doi.org/10.1128/mbio.00714-17	journal	May 2017
Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection Scholte, Florine E. M.; Hua, Brian L.; Spengler, Jessica R. mBio, Vol. 10, Issue 4 https://doi.org/10.1128/mbio.01065-19	journal	July 2019
Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines Malkowska, Maja; Kokoszynska, Katarzyna; Dymecka, Magdalena Virology Journal, Vol. 10, Issue 1 https://doi.org/10.1186/1743-422x-10-1	journal	January 2013
Predominant Infection of CD150+ Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques de Swart, Rik L.; Ludlow, Martin; de Witte, Lot PLoS Pathogens, Vol. 3, Issue 11 https://doi.org/10.1371/journal.ppat.0030178	journal	November 2007
Crimean-congo haemorrhagic fever in pregnancy and in newborn: A case with a unique clinical course Ünlüsoy-Aksu, A.; Havali, C.; Tapisiz, A. Journal of Obstetrics and Gynaecology, Vol. 34, Issue 4 https://doi.org/10.3109/01443615.2013.874984	journal	January 2014
Viral Load and Crimean-Congo Hemorrhagic Fever Papa, Anna; Drosten, Christian; Bino, Silvia Emerging Infectious Diseases, Vol. 13, Issue 5 https://doi.org/10.3201/eid1305.061588	journal	May 2007
Intracellular Events and Cell Fate in Filovirus Infection Olejnik, Judith; Ryabchikova, Elena; Corley, Ronald B. Viruses, Vol. 3, Issue 8 https://doi.org/10.3390/v3081501	journal	August 2011
Pathogenesis of Lassa Fever Yun, Nadezhda E.; Walker, David H. Viruses, Vol. 4, Issue 10 https://doi.org/10.3390/v4102031	journal	October 2012
Of Mice and Not Men: Differences between Mouse and Human Immunology Mestas, Javier; Hughes, Christopher C. W. The Journal of Immunology, Vol. 172, Issue 5 https://doi.org/10.4049/jimmunol.172.5.2731	journal	February 2004
Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells Baize, Sylvain; Kaplon, Jérôme; Faure, Caroline The Journal of Immunology, Vol. 172, Issue 5 https://doi.org/10.4049/jimmunol.172.5.2861	journal	February 2004
Viremia and Antibody Response of Small African and Laboratory Animals to Crimean-Congo Hemorrhagic Fever Virus Infection Shepherd, A. J.; Swanepoel, R.; Leman, P. A. The American Journal of Tropical Medicine and Hygiene, Vol. 40, Issue 5 https://doi.org/10.4269/ajtmh.1989.40.541	journal	May 1989
Crimean-Congo Hemorrhagic Fever: Prognostic Factors and the Association of Leukocyte Counts with Mortality Bastug, Aliye; Kayaaslan, Bircan; Kazancioglu, Sumeyye Japanese Journal of Infectious Diseases, Vol. 69, Issue 1 https://doi.org/10.7883/yoken.jjid.2014.566	journal	January 2016
Crimean-Congo haemorrhagic fever Ergönül, Önder The Lancet Infectious Diseases, Vol. 6, Issue 4 https://doi.org/10.1016/S1473-3099(06)70435-2	journal	April 2006
Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice Hawman, David W.; Haddock, Elaine; Meade-White, Kimberly Antiviral Research, Vol. 157 https://doi.org/10.1016/j.antiviral.2018.06.013	journal	September 2018
Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever Bray, Mike; Geisbert, Thomas W. The International Journal of Biochemistry & Cell Biology, Vol. 37, Issue 8 https://doi.org/10.1016/j.biocel.2005.02.018	journal	August 2005
A healthy newborn born to a mother with Crimean-Congo hemorrhagic fever: is there protection from transplacental transmission? Aydemir, Ozge; Erdeve, Omer; Oguz, Serife Suna International Journal of Infectious Diseases, Vol. 14, Issue 5 https://doi.org/10.1016/j.ijid.2009.07.001	journal	May 2010
Crimean-Congo hemorrhagic fever in pregnancy: A systematic review and case series from Russia, Kazakhstan and Turkey Pshenichnaya, Natalia Yurievna; Leblebicioglu, Hakan; Bozkurt, Ilkay International Journal of Infectious Diseases, Vol. 58 https://doi.org/10.1016/j.ijid.2017.02.019	journal	May 2017
Cytokine levels in Crimean-Congo hemorrhagic fever Papa, Anna; Bino, Silva; Velo, Enkelejda Journal of Clinical Virology, Vol. 36, Issue 4 https://doi.org/10.1016/j.jcv.2006.04.007	journal	August 2006
Viraemic transmission of Crimean-Congo haemorrhagic fever virus to ticks Shepherd, A. J.; Swanepoel, R.; Shepherd, S. P. Epidemiology and Infection, Vol. 106, Issue 2 https://doi.org/10.1017/S0950268800048524	journal	April 1991
Exotic emerging viral diseases: progress and challenges Geisbert, Thomas W.; Jahrling, Peter B. Nature Medicine, Vol. 10, Issue S12 https://doi.org/10.1038/nm1142	journal	November 2004
Molecular Evidence of Sexual Transmission of Ebola Virus Mate, Suzanne E.; Kugelman, Jeffrey R.; Nyenswah, Tolbert G. New England Journal of Medicine, Vol. 373, Issue 25 https://doi.org/10.1056/NEJMoa1509773	journal	December 2015
The Clinical Pathology of Crimean-Congo Hemorrhagic Fever Swanepoel, R.; Gill, D. E.; Shepherd, A. J. Clinical Infectious Diseases, Vol. 11, Issue Supplement_4 https://doi.org/10.1093/clinids/11.Supplement_4.S794	journal	May 1989
Lethal Crimean-Congo Hemorrhagic Fever Virus Infection in Interferon α/β Receptor Knockout Mice Is Associated With High Viral Loads, Proinflammatory Responses, and Coagulopathy Zivcec, Marko; Safronetz, David; Scott, Dana The Journal of Infectious Diseases, Vol. 207, Issue 12 https://doi.org/10.1093/infdis/jit061	journal	February 2013
Review Article 1: The Epidemiology of Tick-Borne Crimean-Congo Hemorrhagic Fever in Asia, Europe, and Africa23 Hoogstraal, Harry Journal of Medical Entomology, Vol. 15, Issue 4 https://doi.org/10.1093/jmedent/15.4.307	journal	May 1979
Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited Ergonul, O.; Celikbas, A.; Baykam, N. Clinical Microbiology and Infection, Vol. 12, Issue 6 https://doi.org/10.1111/j.1469-0691.2006.01445.x	journal	June 2006
Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever Saksida, A.; Duh, D.; Wraber, B. Clinical and Vaccine Immunology, Vol. 17, Issue 7 https://doi.org/10.1128/CVI.00530-09	journal	May 2010
Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells Connolly-Andersen, A. -M.; Moll, G.; Andersson, C. Journal of Virology, Vol. 85, Issue 15 https://doi.org/10.1128/JVI.02469-10	journal	June 2011
Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry Martinez, O.; Johnson, J. C.; Honko, A. Journal of Virology, Vol. 87, Issue 7 https://doi.org/10.1128/JVI.02695-12	journal	January 2013
In Vivo Imaging of Influenza Virus Infection in Immunized Mice Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W. mBio, Vol. 8, Issue 3 https://doi.org/10.1128/mBio.00714-17	journal	May 2017
Favorable Outcomes for both Mother and Baby Are Possible in Pregnant Women with Crimean-Congo Hemorrhagic Fever Disease: A Case Series and Literature Review Gozel, Mustafa Gokhan; Elaldi, Nazif; Engin, Aynur Gynecologic and Obstetric Investigation, Vol. 77, Issue 4 https://doi.org/10.1159/000360699	journal	January 2014
Recombinant Hendra viruses expressing a reporter gene retain pathogenicity in ferrets Marsh, Glenn A.; Virtue, Elena R.; Smith, Ina Virology Journal, Vol. 10, Issue 1 https://doi.org/10.1186/1743-422X-10-95	journal	March 2013
Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin Bergeron, Éric; Zivcec, Marko; Chakrabarti, Ayan K. PLOS Pathogens, Vol. 11, Issue 5 https://doi.org/10.1371/journal.ppat.1004879	journal	May 2015
Interactions of Human Dermal Dendritic Cells and Langerhans Cells Treated with Hyalomma Tick Saliva with Crimean-Congo Hemorrhagic Fever Virus Rodriguez, Sergio; McAuley, Alexander; Gargili, Aysen Viruses, Vol. 10, Issue 7 https://doi.org/10.3390/v10070381	journal	July 2018
Type I IFN Negatively Regulates CD8⁺T Cell Responses through IL-10-Producing CD4⁺T Regulatory 1 Cells Dikopoulos, Nektarios; Bertoletti, Antonio; Kröger, Andrea The Journal of Immunology, Vol. 174, Issue 1 https://doi.org/10.4049/jimmunol.174.1.99	journal	December 2004
Crimean-Congo Hemorrhagic Fever: Prognostic Factors and the Association of Leukocyte Counts with Mortality Bastug, Aliye; Kayaaslan, Bircan; Kazancioglu, Sumeyye Japanese Journal of Infectious Diseases, Vol. 69, Issue 1 https://doi.org/10.7883/yoken.JJID.2014.566	journal	January 2016

Cited By (2)

Additional file 1 of Comparative characterization of Crimean-Congo hemorrhagic fever virus cell culture systems with application to propagation and titration methods Li, Hongzhao; Smith, Greg; Goolia, Melissa figshare https://doi.org/10.6084/m9.figshare.23543290	dataset	January 2023
Additional file 2 of Comparative characterization of Crimean-Congo hemorrhagic fever virus cell culture systems with application to propagation and titration methods Li, Hongzhao; Smith, Greg; Goolia, Melissa figshare https://doi.org/10.6084/m9.figshare.23543293.v1	dataset	January 2023

Similar Records

Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

Journal Article · Wed Jan 06 23:00:00 EST 2016 · PLoS Neglected Tropical Diseases (Online) · OSTI ID:1376846

Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38

Journal Article · Tue Mar 31 00:00:00 EDT 2020 · Journal of Virology · OSTI ID:1839757

Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model

Journal Article · Mon May 20 00:00:00 EDT 2024 · Virus Research · OSTI ID:2471343

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
cytokines
flow cytometry
immunostaining
liver
lymph nodes
macrophages
mouse models
spleen