In a paper published online in advance in Science this week, a team led by investigators at the Johns Hopkins Kimmel Cancer Center shows that the "DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors," or PanNETs. By sequencing the exomes of 10 non-familial PanNETs and then screening for "the most commonly mutated genes in 58 additional PanNETs," the team found that 44 percent of the tumors had somatic inactivating mutations in MEN-1, 43 percent had mutations in genes that encode DAXX and ATRK (two subunits of a transcription/chromatin remodeling complex), and 14 percent had mTOR pathway gene mutations.
Researchers in France and Portugal report in a Science paper published online this week that the interplay between lntA-BAHD1 — a secreted listerial virulence factor and chromatin repressor, respectively — "may modulate IFN [interferon]-λ-mediated immune response to control bacterial colonization of the host" in Listeria monocytogenes infection. "In cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs [interferon-stimulating genes] and stimulated their expression," the authors write. In BAHD1+/– mice, the researchers report that they observed decreased listeriosis and the constitutive expression of lntA.
In this week's issue, a team led by investigators at the University of North Carolina, Chapel Hill, shows that the Kaposi's sarcoma-associated herpesvirus Orf63 "is a viral homolog of human NLRP1," and that it encodes nucleotide binding and oligomerization, leucine-rich repeat proteins, or NLRs. More specifically, the team observed that "Orf63 blocked NLRP1-dependent innate immune responses" and suggests that "modulation of NLR-mediated innate immunity is important for the lifelong persistence of herpesviruses."
And in Science Translational Medicine this week, investigators at Colorado State University and the Beckman Research Institute of the City of Hope show that "an aptamer-siRNA chimera suppresses HIV-1 viral loads and protects from helper CD4+ T cell decline in humanized mice." The team's combinatorial therapeutic approach, in which "an RNA aptamer, with high binding affinity to the HIV-1 envelope (gp120) protein and virus neutralization properties, is attached to and delivers a small interfering RNA that triggers sequence-specific degradation of HIV RNAs," showed a "significantly longer antiviral effect" than observed with the aptamer alone. The aptamer-siRNA, therefore, is an "attractive, nontoxic therapeutic approach for treatment of HIV infection," the authors write.