|Home | About | Journals | Submit | Contact Us | Français|
Retrovirus proteins are translated from either unspliced or spliced mRNAs derived from a single transcript. Gag and Pol proteins are translated from unspliced viral RNA, which is also packaged into virions. Complex retroviruses encode regulatory proteins that transport unspliced viral RNAs to the cytoplasm by interacting with RNA response elements. Other retroviruses carry constitutive transport elements that bind cellular factors for transport of unspliced RNA. Hofacre et al. (p. 12483-12498) show that the betaretrovirus Jaagsiekte sheep retrovirus encodes a regulatory factor (Rej) that is essential for expression of Gag from unspliced viral RNA. Rej acts to facilitate translation of unspliced viral RNA, although in 293T cells it also enhances unspliced RNA export. Nitta et al. (p. 12499-12511) define a Rej response element (RejRE) in the 3′ end of the viral RNA that is likely bound by Rej protein. These findings extend the range of options available to retroviruses to regulate translation.
Flaviviruses assemble in the host cell into an immature particle that requires proteolytic activation to prime its fusion potential. Yu et al. (p. 12101-12107) show that proteolytic cleavage by itself does not cause structural changes. Instead, the environment of the secretory pathway regulates the structure of progeny virus and thereby inhibits the virus from reinfecting the host cell. Only upon release from the producer cell is the virus competent to mediate fusion. These results enhance an understanding of the pathway of flavivirus assembly, transport, maturation, and egress.
Merkel cell polyomavirus (MCV) is a newly discovered tumor virus that is replication defective in cancer cells. Kwun et al. (p. 12118-12128) identify the minimal MCV replication origin and map DNA sites bound by the MCV T antigen. A naturally occurring point mutation in an origin sequence derived from a human tumor, in addition to the previously described large T-antigen mutations, abolishes viral replication origin function. This work shows that cancers caused by MCV are biologic accidents resulting in part from mutations in the viral replication machinery.
The herpes simplex virus 1 (HSV-1) virulence factor ICP34.5 prevents induction of an innate antiviral state. ICP34.5 also inhibits autophagy, a conserved pathway that targets both self and foreign cytoplasmic constituents for lysosomal degradation. ICP34.5 promotes virulence by inhibition of autophagy, although the mechanism by which autophagy regulates HSV virulence is unknown. Leib et al. (p. 12164-12171) demonstrate that ICP34.5 inhibits CD4+ T-cell activation through its interaction with an essential autophagy protein. These studies suggest that in addition to controlling innate responses, ICP34.5 also regulates the host adaptive immune response to HSV-1 through manipulation of the autophagy pathway.
Chronic infection with hepatitis C virus (HCV) causes hepatocellular carcinoma and may contribute to B-cell lymphoma. Machida et al. (p. 12590-12600) now show that HCV infection induces chromosomal polyploidy in hepatocytes and B cells, which is a hallmark of malignancy. Development of polyploidy is due to inhibition of mitotic checkpoint function induced by HCV or the viral core protein alone. This effect is mediated by the alteration of Mad2 protein levels through reduced Rb protein expression.