No abstract

SUMMARYThe structural polypeptides of two strains of measles virus grown in Vero cells were analysed in SDS-PAGE slab gels. Six major polypeptides were identified with mol. wt. of 79o00, 72ooo, 6oooo, 430o0, 4oooo and 36ooo. The largest polypeptide was sensitive to trypsin digestion and was the dominant glycosylated polypeptide identified when the virus was grown in medium containing 3H-fucose or ZH-glucosamine or when the virus was treated with galactose oxidase and labelled with 3H-sodium borohydride. It is concluded that the 79 ooo mol. wt. polypeptide represents the haemagglutinin. Treatment with non-ionic detergent removed this polypeptide and also the 40oo0 tool. wt. polypeptide from the virus envelope. The 4oooo tool. wt. polypeptide is probably associated with haemolysin and cell fusion activities and is analogous to the F1 of paramyxoviruses. A polypeptide of tool. wt. approx. 2oooo detected after glycoprotein labelling may represent the F2 of measles virus. The 430o0 mol. wt. polypeptide co-migrates with cellular actin and is the only major measles polypeptide that is heavily labelled when the virus is grown on Veto cells prelabelled with 35S-methionine. Thus it may represent cellular actin incorporated into the virus during maturation. The quantity of the 72oo0 mol. wt. polypeptide relative to the other major polypeptides varied considerably in different virus preparations. The role of the polypeptide could not be defined. By analogy with previously published data the 6oooo and 36o00 tool. wt. polypeptides are inferred to represent nucleocapsid and membrane proteins, respectively.

Two hundred fifty patients were entered into a multicenter trial to evaluate the efficacy and toxicity of orally administered acyclovir for treatment of recurrent genital herpes. The

Evidence for an interaction of the membrane (M) protein of Newcastle disease and Sendai viruses with cellular actin was obtained by three different techniques. M protein linked to Sepharose 4B was found to bind actin, but not myoglobin or bovine serum albumin, and to selectively remove actin from a mixture of these three proteins. Sedimentation of a mixture of M protein and F-actin through a sucrose gradient resulted in sedimentation of M protein with actin. Control proteins, bovine serum albumin and cytochrome c, did not sediment with actin. In circular dichroism studies, M protein added to actin in a 1:1 complex resulted in a significant increase in negative ellipticity at 220 nm, which corresponds to an increase in alpha-helix and a decrease in beta-structure and random coil. This is indicative of an interaction between M protein and actin. It is possible that the frequent identification of cellular actin in a number of enveloped viruses may be attributed to the interaction of actin and M protein or its equivalent.

Cytomegalovirus (CMV) encodes multiple microRNAs. While these have been partially characterized in vitro, their relevance to clinical CMV infection has not been evaluated. We analyzed samples from a cohort of solid organ transplant patients with CMV disease (n = 245) for viral microRNA expression. Several CMV microRNAs were readily detectable in patients with CMV disease in variable relative abundance. Expression level generally correlated with DNA viral load and the absence of viral microRNA was associated with faster viral clearance. Detection of hcmv-miR-UL22A-5p at baseline independently predicted the recurrence of CMV viremia upon discontinuation of antiviral therapy (OR 3.024, 95% CI: 1.35-6.8; p = 0.007). A combination of direct mRNA targeting by the microRNA and indirect modulation of gene expression involving isoforms of the transcriptional regulator C-MYC may be responsible for the broad effects seen in the association of gene transcripts with the RNA-induced silencing complex and in global protein expression upon hcmv-miR-UL22A-5p transfection. This novel study of in vivo viral microRNA expression profiles provides unique insight into the complexity of clinical CMV infection following transplantation. We provide evidence that viral microRNAs may have complex effects on gene expression and be associated with specific virologic and clinical outcomes, and thus could be further evaluated as biomarkers.