Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections

Hans Peter Hefti, Michael Frese, Heinrich Landis, Claudio Di Paolo, Adriano Aguzzi, Otto Haller, Jovan Pavlovic

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-α/β). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the β subunit of the IFN-α/β receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA- transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.

Original languageEnglish
Pages (from-to)6984-6991
Number of pages8
JournalJournal of Virology
Volume73
Issue number8
Publication statusPublished - 1 Jan 1999
Externally publishedYes

Fingerprint

La Crosse virus
California encephalitis virus
interferon-beta
Interferon-beta
Virus Diseases
lethal genes
Interferon-alpha
Transgenic Mice
Antiviral Agents
Thogotovirus
Semliki forest virus
mice
infection
Thogoto virus
proteins
Semliki Forest virus
genetically modified organisms
RNA Viruses
Virus Replication
Infection

Cite this

Hefti, Hans Peter ; Frese, Michael ; Landis, Heinrich ; Di Paolo, Claudio ; Aguzzi, Adriano ; Haller, Otto ; Pavlovic, Jovan. / Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections. In: Journal of Virology. 1999 ; Vol. 73, No. 8. pp. 6984-6991.
@article{d0dddfb84dbd493f87753c65ce9cc240,
title = "Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections",
abstract = "The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-α/β). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the β subunit of the IFN-α/β receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA- transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.",
author = "Hefti, {Hans Peter} and Michael Frese and Heinrich Landis and {Di Paolo}, Claudio and Adriano Aguzzi and Otto Haller and Jovan Pavlovic",
year = "1999",
month = "1",
day = "1",
language = "English",
volume = "73",
pages = "6984--6991",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

Hefti, HP, Frese, M, Landis, H, Di Paolo, C, Aguzzi, A, Haller, O & Pavlovic, J 1999, 'Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections', Journal of Virology, vol. 73, no. 8, pp. 6984-6991.

Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections. / Hefti, Hans Peter; Frese, Michael; Landis, Heinrich; Di Paolo, Claudio; Aguzzi, Adriano; Haller, Otto; Pavlovic, Jovan.

In: Journal of Virology, Vol. 73, No. 8, 01.01.1999, p. 6984-6991.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections

AU - Hefti, Hans Peter

AU - Frese, Michael

AU - Landis, Heinrich

AU - Di Paolo, Claudio

AU - Aguzzi, Adriano

AU - Haller, Otto

AU - Pavlovic, Jovan

PY - 1999/1/1

Y1 - 1999/1/1

N2 - The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-α/β). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the β subunit of the IFN-α/β receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA- transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.

AB - The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-α/β). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the β subunit of the IFN-α/β receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA- transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.

UR - http://www.scopus.com/inward/record.url?scp=0032775260&partnerID=8YFLogxK

M3 - Article

VL - 73

SP - 6984

EP - 6991

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -