scholarly journals Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus

2016 ◽  
Vol 54 (3) ◽  
pp. 549-562 ◽  
Author(s):  
T. M. Bell ◽  
C. I. Shaia ◽  
J. J. Bearss ◽  
M. E. Mattix ◽  
K. A. Koistinen ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Lassa Virus

scholarly journals Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus)

2018 ◽  
Author(s):  
David X Liu ◽  
Donna L Perry ◽  
Lisa Evans DeWald ◽  
Yingyun Cai ◽  
Katie R Hagen ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Lassa Virus ◽  
Cavia Porcellus

scholarly journals A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

npj Vaccines ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Derek R. Stein ◽  
Bryce M. Warner ◽  
Geoff Soule ◽  
Kevin Tierney ◽  
Kathy L. Frost ◽  
...  
Keyword(s):  
Virus Infection ◽  
Guinea Pigs ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Vesicular Stomatitis

scholarly journals Pichinde Virus Infection of Outbred Hartley Guinea Pigs as a Surrogate Animal Model for Human Lassa Fever: Histopathological and Immunohistochemical Analyses

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 579 ◽  
Author(s):  
Wun-Ju Shieh ◽  
Shuiyun Lan ◽  
Sherif R. Zaki ◽  
Hinh Ly ◽  
Yuying Liang
Keyword(s):  
Animal Model ◽  
Surrogate Model ◽  
Guinea Pigs ◽  
Virulent Strain ◽  
Small Animal ◽  
Immunohistochemical Analysis ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Pichinde Virus ◽  
Guinea Pig Model

Lassa virus (LASV) is a mammarenavirus (arenavirus) that causes zoonotic infection in humans that can lead to fatal hemorrhagic Lassa fever (LF) disease. Currently, there are no FDA-approved vaccines or therapeutics against LASV. Development of treatments against LF and other related arenavirus-induced hemorrhagic fevers (AHFs) requires relevant animal models that can recapitulate clinical and pathological features of AHF diseases in humans. Laboratory mice are generally resistant to LASV infection, and non-human primates, while being a good animal model for LF, are limited by their high cost. Here, we describe a small, affordable, and convenient animal model that is based on outbred Hartley guinea pigs infected with Pichinde virus (PICV), a mammarenavirus that is non-pathogenic in humans, for use as a surrogate model of human LF. We conducted a detailed analysis of tissue histopathology and immunohistochemical analysis of different organs of outbred Hartley guinea pigs infected with different PICV strains that show differential disease phenotypes and pathologies. Comparing to infection with the avirulent PICV strain (P2 or rP2), animals infected with the virulent strain (P18 or rP18) show extensive pathological changes in different organs that sustain high levels of virus replication. The similarity of tissue pathology and viral antigen distribution between the virulent PICV–guinea pig model and lethal human LASV infection supports a role of this small animal model as a surrogate model of studying human LF in order to understand its pathogenesis and for evaluating potential preventative and therapeutic options against AHFs.

scholarly journals Lassa virus antigen distribution and inflammation in the ear of infected strain 13/N Guinea pigs

2020 ◽  
Vol 183 ◽  
pp. 104928
Author(s):  
Thanhthao Huynh ◽  
Joy M. Gary ◽  
Stephen R. Welch ◽  
JoAnn Coleman-McCray ◽  
Jessica R. Harmon ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Virus Antigen ◽  
Lassa Virus

scholarly journals A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Yingyun Cai ◽  
Masaharu Iwasaki ◽  
Daisuke Motooka ◽  
David X. Liu ◽  
Shuiqing Yu ◽  
...  
Keyword(s):  
Intergenic Region ◽  
Guinea Pigs ◽  
Cultured Cells ◽  
Vaccine Candidate ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Western Africa

ABSTRACT Lassa virus (LASV) poses a significant public health problem within the regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding intergenic region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication. IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding intergenic region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

scholarly journals Treatment of Lassa virus infection in outbred guinea pigs with first-in-class human monoclonal antibodies

2016 ◽  
Vol 133 ◽  
pp. 218-222 ◽  
Author(s):  
Robert W. Cross ◽  
Chad E. Mire ◽  
Luis M. Branco ◽  
Joan B. Geisbert ◽  
Megan M. Rowland ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Virus Infection ◽  
Guinea Pigs ◽  
Lassa Virus ◽  
Human Monoclonal Antibodies

scholarly journals Thioaptamer decoy targeting of AP-1 proteins influences cytokine expression and the outcome of arenavirus infections

2007 ◽  
Vol 88 (3) ◽  
pp. 981-990 ◽  
Author(s):  
Susan M. Fennewald ◽  
Erin P. Scott ◽  
Lihong Zhang ◽  
Xianbin Yang ◽  
Judith F. Aronson ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Viral Infections ◽  
Lassa Virus ◽  
Proof Of Concept ◽  
Macrophage Response ◽  
Pichinde Virus ◽  
Viral Haemorrhagic Fever ◽  
Transcription Factor Proteins ◽  
Normal Macrophage

Viral haemorrhagic fever (VHF) is caused by a number of viruses, including arenaviruses. The pathogenesis is believed to involve dysregulation of cytokine production. The arenaviruses Lassa virus and Pichinde virus have a tropism for macrophages and other reticuloendothelial cells and both appear to suppress the normal macrophage response to virus infection. A decoy thioaptamer, XBY-S2, was developed and was found to bind to AP-1 transcription factor proteins. The P388D1 macrophage-like cell line contains members of the AP-1 family which may act as negative regulators of AP-1-controlled transcription. XBY-S2 was found to bind to Fra-2 and JunB, and enhance the induction of cytokines IL-6, IL-8 and TNF-α, while reducing the binding to AP-1 promoter elements. Administration of XBY-S2 to Pichinde virus-infected guinea pigs resulted in a significant reduction in Pichinde virus-induced mortality and enhanced the expression of cytokines from primary guinea pig macrophages, which may contribute to its ability to increase survival of Pichinde virus-infected guinea pigs. These data demonstrate a proof of concept that thioaptamers can be used to modulate the outcome of in vivo viral infections by arenaviruses by the manipulation of transcription factors involved in the regulation of the immune response.

scholarly journals Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Junki Maruyama ◽  
John T. Manning ◽  
Elizabeth J. Mateer ◽  
Rachel Sattler ◽  
Natalya Bukreyeva ◽  
...  
Keyword(s):  
Public Health ◽  
Sierra Leone ◽  
Guinea Pigs ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
African Countries ◽  
Successful Development ◽  
Public Health Perspective ◽  
Lethal Infection

ABSTRACT Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with “flu-like” symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics. IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.

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