Encephalomyocarditis virus (EMCV) is the prototype member of the cardiovirus genus of picornaviruses. For cardioviruses and the related aphthoviruses, the first protein segment translated from the plus-strand RNA genome is the Leader protein. The aphthovirus Leader (173-201 amino acids) is an autocatalytic papain-like protease that cleaves translation factor eIF-4G to shut off cap-dependent host protein synthesis during infection. The less characterized cardioviral Leader is a shorter protein (67-76 amino acids) and does not contain recognizable proteolytic motifs. Instead, these Leaders have sequences consistent with N-terminal zinc-binding motifs, centrally located tyrosine kinase phosphorylation sites, and C-terminal, acid-rich domains. Deletion mutations, removing the zinc motif, the acid domain, or both domains, were engineered into EMCV cDNAs. In all cases, the mutations gave rise to viable viruses, but the plaque phenotypes in HeLa cells were significantly smaller than for wild-type virus. RNA transcripts containing the Leader deletions had reduced capacity to direct protein synthesis in cell-free extracts and the products with deletions in the acid-rich domains were less effective substrates at the L/P1 site, for viral proteinase 3Cpro. Recombinant EMCV Leader (rL) was expressed in bacteria and purified to homogeneity. This protein bound zinc stoichiometrically, whereas protein with a deletion in the zinc motif was inactive. Polyclonal mouse sera, raised against rL, immunoprecipitated Leader-containing precursors from infected HeLa cell extracts, but did not detect significant pools of the mature Leader. However, additional reactions with antiphosphotyrosine antibodies show that the mature Leader, but not its precursors, is phosphorylated during viral infection. The data suggest the natural Leader may play a role in regulation of viral genome translation, perhaps through a triggering phosphorylation event.

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To the Editor: According to the Centers for Disease Control and Prevention, 5%220% of the US population is infected by the influenza virus annually. The influenza virus commonly affects the respiratory system, but the neuropsychiatric symptoms are often underappreciated. Karl Menninger was one of the first to link neuropsychiatric symptoms in 100 patients with influenza who were admitted with behavioral changes in 1918. 1 The famous 1918 strain of influenza was associated with von Economo's encephalitis lethargica and postencephalitic parkinsonism. 2 In the 1960s, pediatric cases of influenza infections were associated with Reye's syndrome. 2 The influenza A 2009 strain was coupled with an increase in the number of serious cases of acute necrotizing encephalopathy. 2 Primary neurological manifestations appear more commonly in children but can emerge in adults with symptoms of headaches, numbness, paresthesia, weakness, vertigo, decreased alertness, seizures, encephalopathy, and meningismus. Other less common neurologic complications include Guillain-Barré syndrome, aseptic meningitis, and transverse myelitis. 2,3 The influenza virus has also been associated with acute psychosis and the onset of a manic episode. [4][5][6] The following report illustrates a case of a patient with suspected influenza-induced mania.

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