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Article ; Online: Heartland Virus

Emily K. Mantlo / Nicholas J. Haley

Zoonotic Diseases, Vol 3, Iss 16, Pp 188-

An Evolving Story of an Emerging Zoonotic and Vector-Borne Disease

2023 Volume 202

Abstract: Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States and is carried by the Lone Star tick ( ... ...

Abstract	Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States and is carried by the Lone Star tick ( Amblyomma americanum ). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5–10% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum . In addition, the recent 2017 introduction of the Asian longhorned tick ( Haemaphysalis longicornis ) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen.
Keywords	Heartland virus ; bandavirus ; Amblyomma americanum ; Haemaphysalis longicornis ; severe fever with thrombocytopenia syndrome virus ; Animal biochemistry ; QP501-801 ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	590
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Luminore CopperTouch Surface Coating Effectively Inactivates SARS-CoV-2, Ebola Virus, and Marburg Virus

Mantlo, Emily K / Paessler, Slobodan / Seregin, Alexey / Mitchell, Alfred

Antimicrobial agents and chemotherapy

2021 Volume 65, Issue 7, Page(s) e0139020

Abstract: We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The copper and copper-nickel surfaces inactivated 99.9% of Ebola and Marburg ...

Abstract	We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The copper and copper-nickel surfaces inactivated 99.9% of Ebola and Marburg viruses after 30 min, and the copper surfaces inactivated 99% of SARS-CoV-2 in 2 h. These data reveal that Ebola virus, Marburg virus, and SARS-CoV-2 are inactivated by exposure to copper ions, validating Luminore CopperTouch as an efficacious tool for infection control.
MeSH term(s)	COVID-19 ; Ebolavirus ; Hemorrhagic Fever, Ebola/drug therapy ; Hemorrhagic Fever, Ebola/prevention & control ; Humans ; Marburgvirus ; SARS-CoV-2
Language	English
Publishing date	2021-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.01390-20
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Book ; Online: In vitro efficacy of a copper iodine complex PPE disinfectant for SARS-CoV-2 inactivation - Raw Data in CSV

Emily K. Mantlo (3705661) / Slobodan Paessler (8800033)

2020

Abstract: ... disinfectant for SARS-CoV-2 inactivation" by Emily Mantlo, et al (2020). ...

Abstract	This is the raw data set for the paper titled "In vitro efficacy of a copper iodine complex PPE disinfectant for SARS-CoV-2 inactivation" by Emily Mantlo, et al (2020).
Keywords	Virology ; SARS-CoV-2 ; COVID-19 ; PPE ; Disinfection ; Iodine ; Decontamination ; covid19
Publishing date	2020-06-16T21:33:16Z
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Luminore CopperTouch™ surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro.

Mantlo, Emily K / Paessler, Slobodan / Seregin, Alexey / Mitchell, Alfred

medRxiv : the preprint server for health sciences

2020

Abstract: We investigated the ability of Luminore CopperTouch™ copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral ... ...

Abstract	We investigated the ability of Luminore CopperTouch™ copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch™ technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.
Keywords	covid19
Language	English
Publishing date	2020-07-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.05.20146043
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice.

Reyna, Rachel A / Maruyama, Junki / Mantlo, Emily K / Manning, John T / Taniguchi, Satoshi / Makishima, Tomoko / Lukashevich, Igor S / Paessler, Slobodan

Biomedicines

2022 Volume 10, Issue 10

Abstract: Lassa virus (LASV) is a zoonotic virus endemic to western Africa that can cause a potentially lethal and hemorrhagic disease, Lassa fever (LF). Survivors suffer a myriad of sequelae, most notably sudden onset sensorineural hearing loss (SNHL), the ... ...

Abstract	Lassa virus (LASV) is a zoonotic virus endemic to western Africa that can cause a potentially lethal and hemorrhagic disease, Lassa fever (LF). Survivors suffer a myriad of sequelae, most notably sudden onset sensorineural hearing loss (SNHL), the mechanism of which remains unclear. Unfortunately, studies aiming to identify the mechanism of these sequelae are limited due to the biosafety level 4 (BSL4) requirements of LASV itself. ML29, a reassortant virus proposed as an experimental vaccine candidate against LASV, is potentially an ideal surrogate model of LF in STAT1-/- mice due to similar phenotype in these animals. We intended to better characterize ML29 pathogenesis and potential sequelae in this animal model. Our results indicate that while both CD4 and CD8 T cells are responsible for acute disease in ML29 infection, ML29 induces significant hearing loss in a mechanism independent of either CD4 or CD8 T cells. We believe that this model could provide valuable information for viral-associated hearing loss in general.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10102433
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Article ; Online: Machupo Virus with Mutations in the Transmembrane Domain and Glycosylation Sites of the Glycoprotein Is Attenuated and Immunogenic in Animal Models of Bolivian Hemorrhagic Fever.

Mantlo, Emily K / Maruyama, Junki / Manning, John T / Wanninger, Timothy G / Huang, Cheng / Smith, Jeanon N / Patterson, Michael / Paessler, Slobodan / Koma, Takaaki

Journal of virology

2022 Volume 96, Issue 8, Page(s) e0020922

Abstract: Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic ... ...

Abstract	Several highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuates MACV in an interferon alpha/beta and gamma (IFN-α/β and -γ) receptor knockout (R
MeSH term(s)	Animals ; Arenaviruses, New World/genetics ; Arenaviruses, New World/immunology ; Disease Models, Animal ; Glycoproteins/metabolism ; Glycosylation ; Guinea Pigs ; Hemorrhagic Fever, American/immunology ; Hemorrhagic Fever, American/virology ; Junin virus/genetics ; Junin virus/immunology ; Mutation ; Vaccines, Attenuated/immunology ; Viral Vaccines/immunology
Chemical Substances	Glycoproteins ; Vaccines, Attenuated ; Viral Vaccines
Language	English
Publishing date	2022-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00209-22
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Article ; Online: The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation.

Manning, John Tyler / Maruyama, Junki / Wanninger, Timothy / Reyna, Rachel A / Stevenson, Heather L / Peng, Bi-Hung / Mantlo, Emily K / Huang, Cheng / Paessler, Slobodan

Frontiers in immunology

2023 Volume 14, Page(s) 1172792

Abstract: Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. A live attenuated vaccine for human use, called Candid#1, is ... ...

Abstract	Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses.
MeSH term(s)	Humans ; Animals ; Guinea Pigs ; Mice ; Junin virus/genetics ; Macaca mulatta/metabolism ; Glycoproteins/metabolism ; Hemorrhagic Fever, American ; Mutation
Chemical Substances	Glycoproteins
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1172792
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Article ; Online: Potent Antiviral Activities of Type I Interferons to SARS-CoV-2 Infection

Emily K. Mantlo / Natalya Bukreyeva / Junki Maruyama / Slobodan Paessler / Cheng Huang

Abstract: The ongoing historic outbreak of COVID-19 not only constitutes a global public health crisis, but also carries a devastating social and economic impact. The disease is caused by a newly identified coronavirus, Severe Acute Respiratory Syndrome ... ...

Abstract	The ongoing historic outbreak of COVID-19 not only constitutes a global public health crisis, but also carries a devastating social and economic impact. The disease is caused by a newly identified coronavirus, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the remarkable sensitivity of SARS-CoV-2 to recombinant human interferons α and β (IFNα/β). Treatment with IFN-α at a concentration of 50 international units (IU) per milliliter drastically reduces viral titers by 3.4 log or over 4 log, respectively, in Vero cells. The EC50 of IFN-α and IFN-β treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggest that SARS-CoV-2 is more sensitive than many other human pathogenic viruses, including SARS-CoV. Overall, our results demonstrate the potent efficacy of human Type I IFN in suppressing SARS-CoV-2 infection, a finding which could inform future treatment options for COVID-19.
Keywords	covid19
Publisher	biorxiv
Document type	Article ; Online
DOI	10.1101/2020.04.02.022764
Database	COVID19

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Article ; Online: Potent Antiviral Activities of Type I Interferons to SARS-CoV-2 Infection

Mantlo, Emily K. / Bukreyeva, Natalya / Maruyama, Junki / Paessler, Slobodan / Huang, Cheng

bioRxiv

Abstract	The ongoing historic outbreak of COVID-19 not only constitutes a global public health crisis, but also carries a devastating social and economic impact. The disease is caused by a newly identified coronavirus, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the remarkable sensitivity of SARS-CoV-2 to recombinant human interferons α and β (IFNα/β). Treatment with IFN-α at a concentration of 50 international units (IU) per milliliter drastically reduces viral titers by 3.4 log or over 4 log, respectively, in Vero cells. The EC50 of IFN-α and IFN-β treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggest that SARS-CoV-2 is more sensitive than many other human pathogenic viruses, including SARS-CoV. Overall, our results demonstrate the potent efficacy of human Type I IFN in suppressing SARS-CoV-2 infection, a finding which could inform future treatment options for COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-04-05
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.04.02.022764
Database	COVID19

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Article ; Online: The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro

Bukreyeva, Natalya / Mantlo, Emily K. / Sattler, Rachel A. / Huang, Cheng / Paessler, Slobodan / Zeldis, Jerry

bioRxiv

Abstract: The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has ... ...

Abstract	The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has led to the deaths of nearly 300,000 people. No approved vaccines or treatments in the USA currently exist for COVID-19, so there is an urgent need to develop effective countermeasures. The IMPDH inhibitor merimepodib (MMPD) is an investigational antiviral drug that acts as a noncompetitive inhibitor of IMPDH. It has been demonstrated to suppress replication of a variety of emerging RNA viruses. We report here that MMPD suppresses SARS-CoV-2 replication in vitro. After overnight pretreatment of Vero cells with 10 μM of MMPD, viral titers were reduced by 4 logs of magnitude, while pretreatment for 4 hours resulted in a 3-log drop. The effect is dose-dependent, and concentrations as low as 3.3 μM significantly reduced viral titers when the cells were pretreated prior to infection. The results of this study provide evidence that MMPD may be a viable treatment option for COVID-19.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.04.07.028589
Database	COVID19

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