Showing papers on "Dengue virus published in 1973"

Studies on the Pathogenesis of Dengue Infection in Monkeys. II. Clinical Laboratory Responses to Heterologous Infection

Abstract: Laboratory responses to a second inoculation of a dengue virus were studied in 118 rhesus monkeys challenged at intervals of two, six, 12, and 26 weeks. Nine animals received the same virus twice; the others received a heterologous type. A single animal manifested leukocytosis, thrombocytopenia, elevation of prothrombin time, and decrease in complement during an infection due to dengue 2 virus that followed a pimary dengue 4 infection at an interval of three months. A mild thrombocytopenia was significantly correlated with secondary dengue 2 infections. A sharp decrease in total complement was observed early after secondary infection with dengue 2 in six of eight monkeys. In secondary dengue 1 and 4 infections, titers of viremia were depressed, while viremia was not detected after secondary challenge with dengue 3. Peak titers of secondary dengue 2 viremia were 13-fold higher than peak titers in primary dengue 2 infections. The greater production of virus in certain secondary infections due to dengue viruses could be a controlling mechanism in the postulated immunologic injury in dengue shock syndrome in man.

Studies on the Pathogenesis of Dengue Infection in Monkeys. I. Clinical Laboratory Responses to Primary Infection

Abstract: Virologic, serologic, and clinical responses to infection were studied in 122 Macaca mulatta monkeys and 17 monkeys of three other species that were inoculated with dengue 1-4 viruses passaged in tissue culture. Susceptible rhesus monkeys, inoculated with either high (1037-10".pfu) or low (8-50 pfu) doses of virus always developed antibody. Frequently with dengue 2 infection, but less frequently with dengue 1 infection, lymphadenomegaly, depression of leukocyte count, and lymphocytosis were noted. In approximately 90% of infected animals viremia began two to six days after inoculation; 90% of dengue 2 and 4 viremias lasted six days or less; the average duration of dengue 1 viremia was somewhat longer, and of dengue 3 viremia shorter than this. HAI titers to the homologous antigen in convalescent sera were usually twofold higher than titers to heterologous dengue viruses; antibody response to dengue 4 infection was relatively specific. No abnormalities were observed in serial hematocrit, prothrombin time, and determinations of total protein. Levels of complement in serum rose several days after the start of serial bleedings in both infected and control animals. The courses of infection due to dengue viruses are similar in humans and monkeys.

Studies on the Pathogenesis of Dengue Infection in Monkeys. III. Sequential Distribution of Virus in Primary and Heterologous Infections

Abstract: Sequential localization in tissue of dengue viruses was studied in 31 primary and eight secondary infections in rhesus monkeys. In ten animals sacrificed before viremia in primary infection, virus was rapidly disseminated from the inoculation site to regional lymph nodes and then to lymphatic tissue throughout the body. Early in the viremic period virus was recovered only from lymph nodes, while two to three days later there was evidence of dissemination to skin and other tissues. Virus was recovered from skin, lymph nodes, and several leukocyte-rich tissues for three days after the termination of viremia. Sequential tissue studies showed virus in circulating leukocytes, in multiple skin sites, and in the upper respiratory tract at the end or just after the termination of viremia. In preliminary experiments, the rate of recovery of virus from tissues was higher in secondary infection than in primary infection. This study suggests that the amount of intracellular infection increases toward the end of the viremic period, abruptly ending one to two days later. This phenomenon correlates closely with the time of onset of shock in human dengue infection.

Replication of Dengue Virus Type 2 in Aedes albopictus Cell Culture

Abstract: The replication of type 2 dengue (D-2) virus in Aedes albopictus (Aal) mosquito cell cultures differed from that in vertebrate (LLC-MK2) rhesus monkey kidney cells. Virus readily replicated in Aal cells at either 30 or 37 C, but had no apparent effect on the host cell. Persistent infection was established with continual virus production for at least 6 months, although the virulence of progeny virus for both suckling mice and LLC-MK2 cells became attenuated. Density gradient analysis of infected Aal cell supernatant products indicated that only complete virus was released, in contrast to infected LLC-MK2 cells which also released incomplete virus. The surface antigens of the virus produced in Aal cells appeared to be considerably modified in that antiserum to vertebrate cell-produced D-2 virus did not block hemagglutination, whereas anti-Aal cell antiserum did. Virus infectivity could be neutralized by the antiserum to D-2 virus grown in vertebrate cells, however. Virus produced in LLC-MK2 cells did not demonstrate a similar host-cell modification. These results may reflect a difference in the mechanism by which D-2 virus matures in Aal cells.

Arbovirus (dengue type) as a cause of acute myocarditis and pericarditis.

Abstract: The arbovirus (arthropod-borne) comprises a large group, now numbering more than 200 types, of which at least 50 have been associated with disease in man. The best known ones are found in Group A and Group B. They commonly manifest with fever, headache, general and local pain, and less commonly rash and lymphadenopathy. Many virus illnesses have been associated with myocarditis and pericarditis and it is only recently that a large number of potential causes of myocarditis have been appreciated. We wish to report a case of myocarditis with pericarditis caused by dengue virus. Two others are briefly mentioned for one has already been the subject of another communication (Nagaratnam and de Silva, I972).

An epidemic of dengue on Tahiti associated with hemorrhagic manifestations.

Abstract: During the course of an outbreak of dengue type 2 on the island of Tahiti, French Polynesia, severe hemorrhagic disease was observed in an unusual number of patients shortly after the onset of a febrile illness. In at least 33 instances, these hemorrhages were severe enough to require hospitalization and 3 patients died. Gastrointestinal bleeding was the most common type of severe hemorrhage observed and gross hematuria was next most common. The available data suggested that most of the hemorrhagic episodes were etiologically related to dengue virus.

Dengue Virus Infection of Mice: Morphology and Morphogenesis of Dengue Type-2 Virus in Suckling Mouse Neurones

Abstract: In dengue type-2 virus-infected neurones of suckling mice, formation of single-membrane vesicles is observed in the distended cisternae of the endoplasmic reticulum mostly of the perinuclear zone around 72 h after inoculation. Electron-dense 50-nm virus particles are arranged in chains in these distended cisternae; some form small crystalloid aggregates. Aberrant particles of different shapes are also seen in the distended cisternae about the same time that the virus particles appear. Parallel filamentous structures are occasionally observed in the cisternae that contain very few virions, either characteristic or aberrant. Increasing cytopathic changes are present after 75 to 96 h. There is an intense vesicular formation. Large numbers of virions and aberrant particles are seen either in the endoplasmic reticulum cisternae or smooth membrane vesicles. They are spread throughout the neurocytoplasm, extending into the dendrites. Dengue virions which are enclosed in fairly intact membrane-bound vesicles are released during cytolysis of the neurones. Morphogenesis of dengue virus type 2 is discussed.

Group B Arbovirus Structural and Nonstructural Antigens III. Serological Specificity of Solubilized Intracellular Viral Proteins

Abstract: Solubilized nonstructural antigen III from Saint Louis encephalitis (SLE)-Japanese B encephalitis (JBE)-West Nile (WN) and dengue-2 arbovirus-infected pig kidney cells was purified by employing Brij-58 solubilization, organic solvent extraction, and column chromatography. Diethylaminoethyl-cellulose column peak C eluate contained only intracellular viral envelope protein designated antigen I. Antigen I of SLE virus absorbed homologous neutralizing antibody; however, the intracellular nonstructural protein designated antigen III did not. The antigenic relationships of solubilized antigens I and III prepared from SLE, JBE, and WN virus-infected cells were determined by complement-fixation (CF) and immunodiffusion analyses. Solubilized antigen I of each virus cross-reacted broadly with both homologous and heterologous antibody at high antigen concentrations in the CF test. Antigen III of each virus reacted with only homologous antibody by both CF and immunoprecipitation. This study demonstrates that during SLE, JBE, WN, and dengue-2 infections, virus-specific proteins containing both type-specific and group-reactive determinants are synthesized. Antigen III, a nonstructural protein, is serologically virus type specific and may be useful as a type-specific diagnostic reagent. Images

Survival of Dengue virus in post mortem samples of tissues from experimentally infected Rhesus monkeys.

Abstract: Dengue virus was shown to persist at 4° C for at least 96 hours and at room temperature for at least 24 hours in tissues removed from experimentally infected monkeys. Virus could not be recovered from samples of the same tissue stored at -70° C for 1 week.

Cloning of dengue virus type 2 by the direct fluorescent antibody technique.

Abstract: SummaryDengue virus type 2 has been cloned in hamster kidney cells, a noncyto-pathic, noncytocidal virus-cell system, utilizing a direct fluorescent antibody method. A clone is considered to have arisen from the infection of a susceptible cell by a single infectious particle of DEN-2.This work was performed under the sponsorship of the Commission on Viral Infections, Armed Forces Epidemiological Board, and was supported by the U. S. Army Medical Research and Development Command under Contract No. DADA17-69-C-9048 and by Public Health Service Research Grant No. AI-02686 from the National Institute of Allergy and Infectious Diseases. The application of direct fluorescent antibody methods to dengue viruses was achieved by Drs. Robert W. Atchison and J. Jayavasu, who also prepared the conjugated immune ascitic fluids. Most able technical assistance was provided by Alma Tillman, Annie McCoy, Carlie White, and Frances Brisset.

Biophysical and Biochemical Studies of Pichinde Virus

Abstract: Pichinde virus, a member of the arenavirus group, was found to contain single-stranded RNA. The RNA consisted of 5 discernible components corresponding to 31S, 28S, 22S, 18S and 4 to 6S. The 28S and 18S RNA’s appeared to be of host cell origin and the 4 to 6S RNA was probably from the same source. The 31S and 22S RNA’s appeared to be components which coded for viral products. The virus was found to contain 4 structural polypeptides. Two were glycopeptides and 2 were polypeptides. One polypeptide (VI) and 1 glycopeptide (VII) remained associated with the viral RNA after treating the virus with nonionic detergent, while the other glycopeptide (VIII) was removed with such treatment. VIV was a minor peptide and its fate following treatment of the virus with nonionic detergent could not be determined.