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Infection of type I interferon receptor-deficient mice with various old world arenaviruses: a model for studying virulence and host species barriers.

Rieger T, Merkler D, Günther S - PLoS ONE (2013)

Bottom Line: Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture.Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung.In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.

ABSTRACT
Lassa virus causes hemorrhagic Lassa fever in humans, while the related Old World arenaviruses Mopeia, Morogoro, and Mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. Here, we studied whether the virulence of Old World arenaviruses in humans and non-human primates is reflected in type I interferon receptor deficient (IFNAR(-/-)) mice by testing several strains of Lassa virus vs. the apathogenic viruses Mopeia, Morogoro, and Mobala. All Lassa virus strains tested-Josiah, AV, BA366, and Nig04-10-replicated to high titers in blood, lung, kidney, heart, spleen, brain, and liver and caused disease as evidenced by weight loss and elevation of aspartate and alanine aminotransferase (AST and ALT) levels with a high AST/ALT ratio. Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture. Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung. In contrast, Mopeia, Morogoro, and Mobala virus replicated poorly in the animals and acute inflammatory alterations were not noted. Depletion of CD4(+) and CD8(+) T cells strongly enhanced susceptibility of IFNAR(-/-) mice to the apathogenic viruses. In conclusion, the virulence of Old World arenaviruses in IFNAR(-/-) mice correlates with their virulence in humans and non-human primates. In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species. The observation that Lassa virus overcomes the species barrier without artificial depletion of T cells suggests it is able to impair T cell functionality in a way that corresponds to depletion.

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Virus titers in organs of IFNAR-/- mice.Animals were inoculated i.v. with 103 FFU of the indicated viruses and euthanized at day 9–10 p.i. to collect the organs. Mean and range are shown (n = 2).
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pone-0072290-g002: Virus titers in organs of IFNAR-/- mice.Animals were inoculated i.v. with 103 FFU of the indicated viruses and euthanized at day 9–10 p.i. to collect the organs. Mean and range are shown (n = 2).

Mentions: Lassa virus is pantropic in humans and other animal models [23,25]. To determine the organ tropism of Lassa, Mopeia, Morogoro, and Mobala virus in IFNAR-/- mice, animals were sacrificed 9 or 10 days p.i. and the virus titer in lung, kidney, heart, spleen, brain, and liver was determined. Lassa virus was detected in all organs with titers ranging from 5 to 7.5 log10 FFU/g tissue (Figure 2). The highest titer was found in lung with about 7 log10 FFU/g tissue. The organ titers for Mopeia, Morogoro, and Mobala virus were generally lower than for Lassa virus. In agreement with the data on viremia, Mopeia virus was found in all organs with titers ranging from 2 to 5.5 log10 FFU/g tissue, while Morogoro and Mobala virus were found only in some organs with titers lower than 2.5 log10 FFU/g tissue (Figure 2). The organ distribution of Mopeia virus differed from that of Lassa virus. In particular, the Mopeia virus titer in brain was much lower compared to the titers in other organs. Taken together, Lassa virus is pantropic in IFNAR-/- mice. The organ titers are consistent with the level of viremia and markers of disease for the different viruses.


Infection of type I interferon receptor-deficient mice with various old world arenaviruses: a model for studying virulence and host species barriers.

Rieger T, Merkler D, Günther S - PLoS ONE (2013)

Virus titers in organs of IFNAR-/- mice.Animals were inoculated i.v. with 103 FFU of the indicated viruses and euthanized at day 9–10 p.i. to collect the organs. Mean and range are shown (n = 2).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750052&req=5

pone-0072290-g002: Virus titers in organs of IFNAR-/- mice.Animals were inoculated i.v. with 103 FFU of the indicated viruses and euthanized at day 9–10 p.i. to collect the organs. Mean and range are shown (n = 2).
Mentions: Lassa virus is pantropic in humans and other animal models [23,25]. To determine the organ tropism of Lassa, Mopeia, Morogoro, and Mobala virus in IFNAR-/- mice, animals were sacrificed 9 or 10 days p.i. and the virus titer in lung, kidney, heart, spleen, brain, and liver was determined. Lassa virus was detected in all organs with titers ranging from 5 to 7.5 log10 FFU/g tissue (Figure 2). The highest titer was found in lung with about 7 log10 FFU/g tissue. The organ titers for Mopeia, Morogoro, and Mobala virus were generally lower than for Lassa virus. In agreement with the data on viremia, Mopeia virus was found in all organs with titers ranging from 2 to 5.5 log10 FFU/g tissue, while Morogoro and Mobala virus were found only in some organs with titers lower than 2.5 log10 FFU/g tissue (Figure 2). The organ distribution of Mopeia virus differed from that of Lassa virus. In particular, the Mopeia virus titer in brain was much lower compared to the titers in other organs. Taken together, Lassa virus is pantropic in IFNAR-/- mice. The organ titers are consistent with the level of viremia and markers of disease for the different viruses.

Bottom Line: Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture.Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung.In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.

ABSTRACT
Lassa virus causes hemorrhagic Lassa fever in humans, while the related Old World arenaviruses Mopeia, Morogoro, and Mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. Here, we studied whether the virulence of Old World arenaviruses in humans and non-human primates is reflected in type I interferon receptor deficient (IFNAR(-/-)) mice by testing several strains of Lassa virus vs. the apathogenic viruses Mopeia, Morogoro, and Mobala. All Lassa virus strains tested-Josiah, AV, BA366, and Nig04-10-replicated to high titers in blood, lung, kidney, heart, spleen, brain, and liver and caused disease as evidenced by weight loss and elevation of aspartate and alanine aminotransferase (AST and ALT) levels with a high AST/ALT ratio. Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture. Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung. In contrast, Mopeia, Morogoro, and Mobala virus replicated poorly in the animals and acute inflammatory alterations were not noted. Depletion of CD4(+) and CD8(+) T cells strongly enhanced susceptibility of IFNAR(-/-) mice to the apathogenic viruses. In conclusion, the virulence of Old World arenaviruses in IFNAR(-/-) mice correlates with their virulence in humans and non-human primates. In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species. The observation that Lassa virus overcomes the species barrier without artificial depletion of T cells suggests it is able to impair T cell functionality in a way that corresponds to depletion.

Show MeSH
Related in: MedlinePlus