Lassa virus infection in experimentally infected marmosets

Liver pathology and immunophenotypic alterations in target tissues

Ricardo Carrion, Kathleen Brasky, Keith Mansfield, Curtis Johnson, Monica Gonzales, Anysha Ticer, Igor Lukashevich, Suzette Tardif, Jean Patterson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

Original languageEnglish (US)
Pages (from-to)6482-6490
Number of pages9
JournalJournal of Virology
Volume81
Issue number12
DOIs
StatePublished - Jun 2007

Fingerprint

Lassa virus
Lassa Fever
Callithrix
Callitrichidae
Virus Diseases
fever
Callithrix jacchus
Pathology
liver
Liver
necrosis
Necrosis
HLA-DP Antigens
Biological Warfare Agents
infection
HLA-DQ Antigens
Interstitial Nephritis
nephritis
Western Africa
Viremia

ASJC Scopus subject areas

  • Immunology

Cite this

Carrion, R., Brasky, K., Mansfield, K., Johnson, C., Gonzales, M., Ticer, A., ... Patterson, J. (2007). Lassa virus infection in experimentally infected marmosets: Liver pathology and immunophenotypic alterations in target tissues. Journal of Virology, 81(12), 6482-6490. https://doi.org/10.1128/JVI.02876-06

Lassa virus infection in experimentally infected marmosets : Liver pathology and immunophenotypic alterations in target tissues. / Carrion, Ricardo; Brasky, Kathleen; Mansfield, Keith; Johnson, Curtis; Gonzales, Monica; Ticer, Anysha; Lukashevich, Igor; Tardif, Suzette; Patterson, Jean.

In: Journal of Virology, Vol. 81, No. 12, 06.2007, p. 6482-6490.

Research output: Contribution to journalArticle

Carrion, R, Brasky, K, Mansfield, K, Johnson, C, Gonzales, M, Ticer, A, Lukashevich, I, Tardif, S & Patterson, J 2007, 'Lassa virus infection in experimentally infected marmosets: Liver pathology and immunophenotypic alterations in target tissues', Journal of Virology, vol. 81, no. 12, pp. 6482-6490. https://doi.org/10.1128/JVI.02876-06
Carrion, Ricardo ; Brasky, Kathleen ; Mansfield, Keith ; Johnson, Curtis ; Gonzales, Monica ; Ticer, Anysha ; Lukashevich, Igor ; Tardif, Suzette ; Patterson, Jean. / Lassa virus infection in experimentally infected marmosets : Liver pathology and immunophenotypic alterations in target tissues. In: Journal of Virology. 2007 ; Vol. 81, No. 12. pp. 6482-6490.
@article{2598ab281fff4e69a5c968a720981286,
title = "Lassa virus infection in experimentally infected marmosets: Liver pathology and immunophenotypic alterations in target tissues",
abstract = "Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.",
author = "Ricardo Carrion and Kathleen Brasky and Keith Mansfield and Curtis Johnson and Monica Gonzales and Anysha Ticer and Igor Lukashevich and Suzette Tardif and Jean Patterson",
year = "2007",
month = "6",
doi = "10.1128/JVI.02876-06",
language = "English (US)",
volume = "81",
pages = "6482--6490",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Lassa virus infection in experimentally infected marmosets

T2 - Liver pathology and immunophenotypic alterations in target tissues

AU - Carrion, Ricardo

AU - Brasky, Kathleen

AU - Mansfield, Keith

AU - Johnson, Curtis

AU - Gonzales, Monica

AU - Ticer, Anysha

AU - Lukashevich, Igor

AU - Tardif, Suzette

AU - Patterson, Jean

PY - 2007/6

Y1 - 2007/6

N2 - Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

AB - Lassa virus causes thousands of deaths annually in western Africa and is considered a potential biological weapon. In an attempt to develop a small nonhuman primate model of Lassa fever, common marmosets were subcutaneously inoculated with Lassa virus strain Josiah. This inoculation resulted in a systemic disease with clinical and morphological features mirroring those in fatal human Lassa infection: fever, weight loss, high viremia and viral RNA load in tissues, elevated liver enzymes, and severe morbidity between days 15 and 20. The most prominent histopathology findings included multifocal hepatic necrosis with mild inflammation and hepatocyte proliferation, lymphoid depletion, and interstitial nephritis. Cellular aggregates in regions of hepatocellular necrosis were largely composed of HAM56-positive macrophages, devoid of CD3-positive and CD20-positive cells, and characterized by marked reductions in the intensity of HLA-DP, DQ, DR staining. A marked reduction in the major histocompatibility complex class II expression was also observed in the lymph nodes. Immunophenotypic alterations in spleen included reductions in overall numbers of CD20-positive and CD3-positive cells and the disruption of lymphoid follicular architecture. These findings identify the common marmoset as an appropriate model of human Lassa fever and present the first experimental evidence that replication of Lassa virus in tissues is associated with alterations that would be expected to impair adaptive immunity.

UR - http://www.scopus.com/inward/record.url?scp=34249952426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249952426&partnerID=8YFLogxK

U2 - 10.1128/JVI.02876-06

DO - 10.1128/JVI.02876-06

M3 - Article

VL - 81

SP - 6482

EP - 6490

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -