Powassan virus (POWV) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between Ixodes cookei and other ixodid ticks and small and medium-sized mammals. During 1958-1998, only 27 POWV disease cases (mostly Powassan encephalitis) were reported from eastern Canada and the northeastern United States (average, 0.7 cases per year). During 1999-2005, nine cases (described herein) of serologically confirmed POWV disease were reported in the United States (average, 1.3 cases per year): four from Maine, two from New York, and one each from Michigan, Vermont, and Wisconsin. The Michigan and Wisconsin cases are the first ever reported from the north-central United States. Of these nine patients, 5 (56%) were men, the median age was 69 years (range: 25-91 years), and 6 (67%) had onset during May-July. All but one patient developed encephalitis with acute onset of profound muscle weakness, confusion, and other severe neurologic signs. In one case, no neurologic symptoms were present but the presence of pleocytosis, an elevated cerebrospinal fluid (CSF) protein concentration, and POWV-specific immunoglobulin M in CSF suggested neuroinvasion. All patients recovered from their acute disease, but most had long-term neurologic sequelae. Periresidential ecologic investigations were performed in three cases, including tests of local mammals and ticks for evidence of POWV infection. Woodchucks (Marmota monax), striped skunks (Mephitis mephitis), and a raccoon (Procyon lotor) collected at two of the Maine case-patients' residences had neutralizing antibody titers to POWV. I. cookei were found on woodchucks and skunks and questing in grassy areas of one of these residences; all were negative for POWV. Although POWV disease is rare, it is probably under-recognized, and it causes significant morbidity, and thus is an additional tick-borne emerging infectious disease entity. Because no vaccine or specific therapy is available, the basis of prevention is personal protection from ticks (or "tick hygiene") and reduced exposure to peridomestic wild mammals.
SUMMARYWe have examined the expression of type C RNA viruses in different Friend erythroleukaemic cell types, distinguished on the basis of increasingly malignant characteristics, which arise during the ageing of mice inoculated with the polycythaemic Friend virus complex. Most early appearing Friend cells (type I) expressed ecotropic virus, but cells of later malignant types showed decreased and variable expression. In general, the more malignant cells released less ecotropic virus. Xenotropic virus was detected in low numbers from type I, II, and IV cells. Two viruses were cloned from type II tumour cells: a xenotropic virus (II clone l) and an N-tropic ecotropic virus (II clone 2). No pathogenic activity was found when II clone 1 was inoculated into newborn and adult DBA/2J and NIH/Swiss mice observed for up to 20 months, whereas II clone 2 caused a rapid anaemic erythroleukaemia in both N-and B-type newborn mouse strains. It caused a similar form of leukaemia in susceptible N-type adult mice, but at a lower frequency and with a longer latency (usually >5 months). This finding demonstrated a lack of NB restriction in newborn mice. The virus was much less active in DBA/2J mice from which it had been originally cloned; it also appeared to cause lymphoma or to shorten the latency of spontaneous lymphoma in DBA/2J mice.
We examined the expression of cytochemical markers of myeloid and monocyte-macrophage differentiation in conjunction with ultrastructural studies of different malignant erythroleukemic cells isolated from mice infected with the Friend polycythemic virus complex (FLV-P). The amounts of fluoride-sensitive and resistant nonspecific esterase activity increased with the progression of malignancy. Isoelectric focusing resolved this enzyme activity into 13 isozymes in the most malignant Friend cell type tested. These same isozymes were found in the adherent cell population of normal spleens. Two of these isozymes were shown to have chloroacetate esterase activity characteristic of granulocytes. Despite these myeloid and monocyte characteristics, light and electron microscopy showed no morphological evidence of differentiation in either of these lineages. This study demonstrates that the Friend erythroleukemic cell contains markers of three different hemopoietic cell types. The expression of myeloid, monocytic, and erythroid traits in these erythroleukemic cells can be used to monitor their malignant progression.
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