An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity.

Dynamic small ubiquitin-like modifier (SUMO) linkages to diverse cellular protein groups are critical to orchestrate resolution of stresses such as genome damage, hypoxia, or proteotoxicity. Defense against pathogen insult (often reliant upon host recognition of "non-self" nucleic acids) is also modulated by SUMO, but the underlying mechanisms are incompletely understood. Here, we used quantitative SILAC-based proteomics to survey pan-viral host SUMOylation responses, creating a resource of almost 600 common and unique SUMO remodeling events that are mounted during influenza A and B virus infections, as well as during viral innate immune stimulation.

Human MxB Protein Is a Pan-herpesvirus Restriction Factor.

Herpesvirus infections are highly prevalent in the human population and persist for life. They are often acquired subclinically but potentially progress to life-threatening diseases in immunocompromised individuals. The interferon system is indispensable for the control of herpesviral replication.

Human interactome of the influenza B virus NS1 protein.

NS1 proteins of influenza A and B viruses share limited sequence homology, yet both are potent manipulators of host cell processes, particularly interferon (IFN) induction. Although many cellular partners are reported for A/NS1, only a few (e.g.

Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses.

Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon.

Structural requirements for the antiviral activity of the human MxA protein against Thogoto and influenza A virus.

The interferon-induced dynamin-like MxA protein has broad antiviral activity against many viruses, including orthomyxoviruses such as influenza A and Thogoto virus and bunyaviruses such as La Crosse virus. MxA consists of an N-terminal globular GTPase domain, a connecting bundle signaling element, and the C-terminal stalk that mediates oligomerization and antiviral specificity. We previously reported that the disordered loop L4 that protrudes from the compact stalk is a key determinant of antiviral specificity against influenza A and Thogoto virus.

Evolution-guided identification of antiviral specificity determinants in the broadly acting interferon-induced innate immunity factor MxA.

MxA is an interferon-induced dynamin-like GTPase with wide-ranging antiviral activity, which hinges upon detection of unique viral structures that differ across virus families. Despite elucidation of its structure, the basis of MxA antiviral specificity remains enigmatic. We used an evolution-guided approach to identify the loop L4 of MxA as a hotspot for recurrent positive selection in primates.

Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells.

Influenza B virus infections are mainly restricted to humans, which is partially caused by the inability of influenza B virus NS1 protein to counteract the innate immune response of other species. However, for cell culture-based influenza vaccine production non-human cells, such as Madin-Darby canine kidney (MDCK) cells, are commonly used. Therefore, the impact of cellular pathogen defence mechanisms on influenza B virus propagation in MDCK cells was analysed in this study.