Replication of Colorado tick fever virus within human hematopoietic progenitor cells.

Significant neutropenia, as well as thrombocytopenia and a mild anemia, occurs in patients infected with Colorado tick fever virus. In this study, human bone marrow CD34+ cells and KG-1a cells, a human hematopoietic progenitor cell line, were infected in vitro with Colorado tick fever virus. The time course and morphological appearance of viral replication in human progenitor cells were similar to those seen in erythroblasts and in HEL cells and suggest one possible mechanism for the clinical hematologic findings.

Inhibition of bluetongue and Colorado tick fever orbiviruses by selected antiviral substances.

The effects of four ribonucleic acid virus inhibitors were evaluated in cell cultures and in mice to determine inhibitory effects against bluetongue virus and Colorado tick fever virus (CTFV). Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine, 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine. Ribavirin-2',3',5'-triacetate (ribavirin triacetate) was evaluated in vivo against CTFV. Inhibition of cytopathic effect and plaque reduction were used to evaluate antiviral activity. In cytopathic effect inhibition studies, bluetongue virus was markedly inhibited by 3-deazaguanine and 3-deazauridine in Vero cells with moderate inhibition by the other agents. Ribavirin and 3-deazaguanine markedly inhibited CTFV in MA-104 cells, 3-deazauridine was slightly less active, and 9-(S)-(2,3-dihydroxypropyl)adenine was negative. Ribavirin was less effective in Vero cells against CTFV. When mice were inoculated intracerebrally with CTFV and treated by a single intracerebral injection with drug, ribavirin triacetate increased the number of survivors, 3-deazaguanine increased mean survival time, and ribavirin was negative. Intraperitoneal treatment of infected mice with ribavirin triacetate for 1 week significantly increased the number of survivors and mean survival time, providing strong evidence that the agent is active across the blood-brain barrier.

Discriminant analysis: a method of identifying foci of vector-borne diseases.

Identification of foci of vector-borne diseases does not require knowledge of exact abundances of vectors and pathogens; rather, a focus is defined by the presence, or some minimal level of abundance, of a vector and pathogen. Stepwise discriminant analysis (DA) was applied to data on free-ranging adult wood ticks (the vector) and to data on isolations of Colorado tick fever virus from small mammals. Trap stations were grouped on the basis of relative abundance of wood ticks for one set of analyses and on the presence or absence of virus for another set of analyses. Additional data consisted of easily measured environmental variables. It is concluded that DA provides a useful tool for analysis of ecosystem structure and an effective means of identifying foci of infection.

The development of Colorado tick fever virus within cells of the haemopoietic system.

Electron microscopic examination of haemopoietic liver tissue from mice infected in utero or when newborn showed inclusions of Colorado tick fever virus within erythroblasts, reticulocytes and erythrocytes. Inclusions were also seen within erythroblastoid cells undergoing mitosis. Other evidence of virus replication within erythropoietic cells was the presence of intracytoplasmic and intranuclear fibres, which have been shown to be associated with Colorado tick fever virus replication. The findings reported here support the hypothesis that virus replication within infected erythropoietic cells occurs concurrently with differentiation of the infected cell, resulting in the presence of virions within erythrocytes.