Saturday, February 26, 2011

(VZV) Entrapment

In this impressively thorough paper from our own backyard, Stanford researchers from Ann Arvin's lab have provided evidence of a newly identified antiviral mechanism that can specifically "entrap"  VZV capsid protein in mature and immature forms in protein "cages." 

                                     Something like that.... only for VZV.

Protomyelocytic leukemia protein (PML) serves as the key structural component of PML-nuclear bodies (PML-NB), which have numerous morphologies and functions in mammalian nuclei. As this group reports, when PML-NBs form into spherical cages in VZV-infected cells, it is possible to observe sequestration of the VZV capsid protein ORF23, as well as immature/mature capsids.

They were able to use extremely high sensitivity cryoimmuno-electron microscopy (cryoimmuno-EM) to determine precisely whether the capsid protein was hed within the PML-NBs both in in vitro cultured cells and in vivo in human Dorsal Rot Ganglia and skin xenographs from  a severe combined immunodeficiency (SCID) mouse model.  They went on to determine that only one of the six PML isoforms, PML IV, possesses this antiviral capacity. As a final accent, they even found that these same PML-NBs were also responsible for sequestering the mutant aggregated protein Huntingtin, the cause of Huntington's disease. Thus, they conclude that PML can function to block viral assembly as well as contain potentially harmful protein aggregates.

- Vy Tran

Reichelt M, Wang L, Sommer M, Perrino J, Nour AM, et al. (2011) Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus. PLoS Pathog 7(2): e1001266. doi:10.1371/journal.ppat.1001266

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