Dataset Information

Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids.

ABSTRACT: Interferon-induced human MxA protein belongs to the dynamin superfamily of large GTPases. It exhibits antiviral activity against a variety of RNA viruses, including Thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks. Here, we report that MxA blocks the transport of Thogoto virus nucleocapsids into the nucleus, thereby preventing transcription of the viral genome. This interaction can be abolished by a mAb that neutralizes the antiviral activity of MxA. Our results reveal an antiviral mechanism whereby an interferon-induced protein traps the incoming virus and interferes with proper transport of the viral genome to its ultimate target compartment within the infected cell.

SUBMITTER: Kochs G

PROVIDER: S-EPMC26740 | biostudies-literature | 1999 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids.

Kochs G G Haller O O

Proceedings of the National Academy of Sciences of the United States of America 19990301 5

Interferon-induced human MxA protein belongs to the dynamin superfamily of large GTPases. It exhibits antiviral activity against a variety of RNA viruses, including Thogoto virus, an influenza virus-like orthomyxovirus transmitted by ticks. Here, we report that MxA blocks the transport of Thogoto virus nucleocapsids into the nucleus, thereby preventing transcription of the viral genome. This interaction can be abolished by a mAb that neutralizes the antiviral activity of MxA. Our results reveal ...[more]

PMID: 10051598

Similar Datasets

Project description:UnlabelledType I interferons (IFNs) crucially contribute to host survival upon viral infections. Robust expression of type I IFNs (IFN-α/β) and induction of an antiviral state critically depend on amplification of the IFN signal via the type I IFN receptor (IFNAR). A small amount of type I IFN produced early upon virus infection binds the IFNAR and activates a self-enhancing positive feedback loop, resulting in induction of large, protective amounts of IFN-α. Unexpectedly, we found robust, systemic IFN-α expression upon infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus (THOV). The IFNAR-independent IFN-α production required in vivo conditions and was not achieved during in vitro infection. Using replication-incompetent THOV-derived virus-like particles, we demonstrate that IFNAR-independent type I IFN induction depends on viral polymerase activity but is largely independent of viral replication. To discover the cell type responsible for this effect, we used type I IFN reporter mice and identified CD11b(+) F4/80(+) myeloid cells within the peritoneal cavity of infected animals as the main source of IFNAR-independent type I IFN, corresponding to the particular tropism of THOV for this cell type.ImportanceType I IFNs are crucial for the survival of a host upon most viral infections, and, moreover, they shape subsequent adaptive immune responses. Production of protective amounts of type I IFN critically depends on the positive feedback amplification via the IFNAR. Unexpectedly, we observed robust IFNAR-independent type I IFN expression upon THOV infection and unraveled molecular mechanisms and determined the tissue and cell type involved. Our data indicate that the host can effectively use alternative pathways to induce type I IFN responses if the classical feedback amplification is not available. Understanding how type I IFN can be produced in large amounts independently of IFNAR-dependent enhancement will identify mechanisms which might contribute to novel therapeutic strategies to fight viral pathogens.

Dataset Information

Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids.

Publications

Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets