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Published on: November 1, 2011
Interferon-induced rat Mx proteins confer resistance to Rift Valley fever virus and other arthropod-borne viruses
M Sandrock1, M Frese, O Haller
1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79104 Freiburg, Germany.
Abstract:
Mx proteins belong to the interferon (IFN)-induced antiviral defense. The rat genome contains three Mx genes, ratMx1, ratMx2, and ratMx3. The Mx gene products differ in their subcellular localization and antiviral specificity. The nuclear ratMx1 protein confers resistance to influenza A virus, and the cytoplasmic ratMx2 is active against vesicular stomatitis virus (VSV), whereas the cytoplasmic ratMx3 protein is antivirally inactive. To investigate the antiviral potential of the rat Mx proteins against arboviruses, a phylogenetically diverse group of viruses that frequently infect rodents, we studied the replication of LaCrosse virus (LACV). Rift Valley fever virus (RVFV) (both family Bunyaviridae), and Thogoto virus (THOV) (family Orthomyxoviridae). To that end, we used transfected Vero cells constitutively expressing one of the rat Mx proteins. We observed that the antiviral activity of rat Mx proteins against these arboviruses correlates with their intracellular localization: ratMx1 is active against THOV, which replicates in the nucleus, whereas ratMx2 inhibits bunyaviruses that replicate in the cytoplasm. The results indicate that rats have evolved two Mx proteins to efficiently control viruses with different replication strategies.
Insights
Rats possess two interferon-induced Mx proteins, ratMx1 and ratMx2, that provide defense against arboviruses. Their antiviral activity depends on intracellular localization, targeting viruses with distinct replication strategies.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mx proteins are interferon-induced antiviral factors.
- Rats have three Mx genes (ratMx1, ratMx2, ratMx3) with varying cellular locations and antiviral specificities.
- Nuclear ratMx1 targets influenza A, while cytoplasmic ratMx2 targets vesicular stomatitis virus.
Purpose of the Study:
- To investigate the antiviral potential of rat Mx proteins against arboviruses.
- To determine if Mx protein localization influences arbovirus inhibition.
- To understand rat Mx protein efficacy against viruses with different replication strategies.
Main Methods:
- Used transfected Vero cells expressing ratMx1, ratMx2, or ratMx3.
- Studied the replication of LaCrosse virus (Bunyaviridae), Rift Valley fever virus (Bunyaviridae), and Thogoto virus (Orthomyxoviridae).
- Correlated Mx protein antiviral activity with their intracellular localization and viral replication sites.
Main Results:
- RatMx1 demonstrated antiviral activity against Thogoto virus, which replicates in the nucleus.
- RatMx2 inhibited bunyaviruses (LaCrosse virus, Rift Valley fever virus) that replicate in the cytoplasm.
- RatMx3 showed no antiviral activity against the tested arboviruses.
Conclusions:
- Rat Mx proteins exhibit arbovirus specificity based on their subcellular localization.
- RatMx1 and RatMx2 are key components of the rat's innate immune defense against arboviruses.
- Rats have evolved distinct Mx proteins to control viruses with diverse replication mechanisms.
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