The isolation and sequence comparison of avirulent and neurovirulent strains of polio virus, alpha virus, herpes virus, immunodeficiency virus, and other viruses have identified genetic changes that are required to cause disease in the nervous system. The molecular mecanisms by which these genetic change result in neurovirulence are unknown. An avirulent laboratory strain of the Alphavirus Sindbis kills most cultured cell lines not by lethal parasitism, but by inducing apoptosis or programmed cell death. Transfection of cultured cells with the human bc1-2 oncogene can block Sindbis virusinduced apoptosis, resulting in a persistent viral infection resembling that observed in brains of immunodefcient mice.We investigated the possibility that neuroVirulent strains of Sindbis virus could overcome the protective effects of bcl-2-a potential mechanism to explain the ability of these strains to cause fatal disease. Strains of Sindbis virus that were lethal for 2-to 4-week-old mice induced apoptotic death in cultured cells despite the presence of bcl-2. (1,17). When SV strain AR339 was serially passaged in mouse brain, NSV was recovered, which caused more severe encephalitis and death in 3-to 4-week-old animals (18). Here we confirm the earlier mortality data and show that mice as young as 2 weeks recover from AR339 but not from NSV infection ( Table 1). The ability of neurovirulent NSV to kill older mice is not facilitated by access to new neural cell types, since neurons remain the primary target cell in the brain for both viruses (19). Therefore, other mechanisms for virulence must be involved. We tested the possiAbbreviations: SV, Sindbis virus; NSV, neuroadapted strain of SV. *To whom reprint requests should be addressed. 5202The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Vancomycin-resistant Enterococcus faecium (VRE) is a common nosocomial isolate, especially among patients with cancer. VRE infections have substantial attributable mortality among patients with cancer. The purpose of this study was to identify risk factors for developing bloodstream infection with VRE in patients with cancer who are colonized with VRE. VRE colonization was prospectively identified in 197 patients with cancer during 4-year period, of whom 179 (91%) had complete records for evaluation. Of these 179 patients, 24 (13.4%) developed hospital-acquired VRE bloodstream infections. Risk factors for VRE bloodstream infection included vancomycin use (relative risk [RR], 1.98; 95% confidence interval [CI], 1.25-3.14), diabetes mellitus (RR, 3.91; 95% CI, 1.20-12.77), gastrointestinal procedures (RR, 4.56; 95% CI, 1.05-19.7), and acute renal failure (RR, 3.10; 95% CI, 1.07-8.93). Strategies for preventing VRE bloodstream infection in VRE-colonized patients with cancer should include limiting vancomycin use and, perhaps, gastrointestinal procedures.

Many alphaviruses cause more severe disease in young animals than in older animals. The age-dependent resistance to severe disease is determined primarily by maturation of the host, but strains of virus can be selected that overcome the increased resistance of mature animals. Sindbis virus (SV) strain AR339 causes fatal encephalitis in newborn mice and nonfatal encephalitis in weanling mice, whereas NSV, a neuroadapted strain of SV, causes fatal encephalitis in weanling as well as newborn mice. We have previously shown that the E2 glycoprotein of NSV contained His-55, whereas AR339 E2 had Gln-55 (S. Lustig, A

The mechanism by which amino acid changes in the E1 and E2 surface glycoproteins of Sindbis virus affect neurovirulence is unknown. We have studied two recombinant viruses which differ in virulence. One (TE) contains Gly and the other (TES) contains Arg at position 172 in E2. TE causes more rapid death than TES in newborn mice. Both viruses replicate similarly in nonneuronal cells, but TE replicates more rapidly in the brains of newborn mice and in neuroblastoma cells. TE also induces earlier viral RNA synthesis in neuroblastoma cells. 35S-labeled TE binds more efficiently to brain and neuroblastoma cells, but not to nonneuronal cells, than TES. We propose that a region of the E2 glycoprotein affected by the amino acid occupying position 172 is important for binding to an alphavirus receptor on neurons and influences neurovirulence by this mechanism.