Role of antibodies and host cells in plaque enhancement of Murray Valley encephalitis virus.

Chicken antisera to Murray Valley encephalitis (MVE) virus, when incubated with virus and assayed for plaques on chicken embryo (CE) monolayers, neutralized MVE virus at high concentrations of antibody, but caused increases in plaque counts at low concentrations of antibody. Plaque enhancement did not occur when the same virus-antibody mixtures were assayed on a continuous line of rhesus monkey kidney cells (LLC-MK2), nor when the anti-MVE antibody was of mammalian origin and the assay system was CE monolayers. Correspondingly, chicken anti-MVE did not enhance the plaque formation of MVE virus in a stable line of mouse macrophages, P-388D1, whereas rabbit and mouse anti-MVE did enhance plaque formation.

Comparison of P388D1 mouse macrophage cell line and human monocytes for assay of dengue-2 infection-enhancing antibodies.

Tissue culture-adapted dengue 2 virus (DEN 2), strain 16681, exhibits antibody-dependent enhancement of infection (ADE) in P388D1 cells, a mouse macrophage-like cell line. ADE is dependent upon maintaining DEN 2 multiplicity of infection at between 0.1 and 0.

Original antigenic sin in dengue.

Sequential blood samples were obtained from eight Thai children before, during and 3-5 months after hospitalization for dengue shock syndrome. All patients experienced a secondary-type antibody response as evidenced by hemagglutination-inhibition antibody responses in acute and convalescent sera. Dengue 2 viruses were recovered from two patients.

Antiviral effects if ribavirin and 6-mercapto-9-tetrahydro-2-furylpurine against dengue viruses in vitro.

The antiviral effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) and 6-mercapto-9-tetrahydro-2-furylpurine (6-MPTF) against dengue viruses were examined in vitro. Ribavirin significantly reduced the growth of dengue virus types 1-4 in LLC-MK2 cells at concentrations well below cytotoxic levels (cell viability was determined by trypan blue dye exclusion) Addition of guanosine to ribavirin-treated dengue virus-infected cell cultures completely reversed the antiviral effect of the drug. In contrast, ribavirin had no effect on dengue virus replication in human peripheral blood leukocytes (PBL).

Rubella antibody persistence after immunization.

A comparative field trial of three live, attenuated rubella virus vaccines (Cendehill, HPV 77 DE-5, and HPV-77 DK-12) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Following initial seroconversion rates of more than 98%, periodic serological testing of the study population was conducted to assess the durability of vaccine-induced immunity. In February 1980, ten years after the initiation of the study, 741 of the 5,153 original susceptible vaccinees were still enrolled in the study.

Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vitro studies.

Various Sephadex G-15 fractions of pepsin-digested mucosal extract inhibited the in vitro association of cholera vibrios with mucosal slices. Inhibitory activity paralleled the taxin activity of the fractions for these bacteria. This supports the theory that inhibition of mucosal association by pepsin-digested mucosal scrapings was due to the blocking of taxin receptors on the bacterial surface.

Propagation of dengue viruses in murine cell cultures.

Dengue viruses were cultivated in Balb 3T12-3 cells, a continuous line of cells derived from mouse embryo cell cultures. Optimal serum concentrations were determined for maximal kinetics of virus replication. All four types of dengue viruses replicate in these cells, and peak virus titers were obtained by 72 hours post-infection.

In vitro virulence marker: growth of dengue-2 virus in human leukocyte suspension cultures.

We wished to find a simple, biologically relevant method to evaluate the virulence of dengue viruses for human beings. Since cells of mononuclear phagocyte lineage may be important sites of dengue infection in primates, we evaluated the permissiveness of these cells to dengue virus as a correlate of virus virulence. Two wild-type, large-plaque, monkey-virulent dengue-2 virus strains and two small-plaque, monkey-avirulent dengue-2 virus strains were evaluated for their ability to replicate in human peripheral blood leukocyte cultures supplemented with enhancing antibody.

Suppression of dengue virus replication in vitro by rimantadine hydrochloride.

The effects of rimantadine on dengue virus replication were examined in a variety of tissue culture systems. The growth of dengue virus type 2 in human peripheral blood leukocytes (PBL) was completely suppressed when rimantadine was included in the culture medium at a concentration of 25 microgram/ml. Similarly, rimantadine caused a significant inhibition of dengue virus replicaton in cultures of rhesus monkey PBL.

Inhibition of dengue virus replication by amantadine hydrochloride.

The effect of amantadine hydrochloride (1-adamantanamine hydrochloride) on dengue virus replication was examined in vitro. Amantadine decreased the titers of all four types of dengue viruses grown in LLC-MK2 cells by greater than 90% at concentrations of 50 micrograms/ml. There was no evidence for any cytopathic effect of the drug at concentrations less than 100 micrograms/ml.

Transmission of dengue 1 and 2 viruses in Greece in 1928.

In August-September 1928 appoximately 650,000 residents of Athens and Piraeus contracted dengue fever, and 1,061 died. We were interested in the etiology of this severe epidemic in which many cases resembled dengue hemorrhagic fever or the dengue shock syndrome, and have attempted a retrospective seroepidemiological study. Serum specimens were obtained from 111 residents of Athens or Piraeus who were born in 1927 or 1928, and were studied by plaque reduction neutralization test for antibodies to dengue 1-4 viruses.

Enhancement of dengue virus infection in monocytes by flavivirus antisera.

Enhanced dengue 2 virus (D2V) infection in suspension cultures of human peripheral blood mononuclear phagocytes (PBL) produced by subneutralizing concentrations of dengue antisera has been described previously. In this study, the enhancement phenomenon was found to be a general property of representative flavivirus antisera. All except one of 24 antisera, which had been raised by 1-3 injections of flaviviruses in rabbits, enhanced the growth of dengue 2 virus in human PBL.

Studies on dengue 2 virus infection in cyclophosphamide-treated rhesus monkeys.

Dengue 2 virus (D2V) replication has been demonstrated in cultured primate mononuclear phagocytes, mitogen treated lymphocytes and lymphoblastoid cells. To determine which of these cell types might play an important role in sustaining infection in vivo, nine rhesus monkeys were immunosuppressed with cyclophosphamide and then infected with D2V. Maintenance dose which held total white blood cell counts to less than 3000/mm3 ablated both primary and secondary antibody responses.

Dengue haemorrhagic fever--a public health problem and a field for research.

Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is an enigmatic and growing public health problem which is confined at present to countries of South-East Asia. Since 1956, over 350 000 patients have been hospitalized and nearly 12 000 deaths have been reported. Dengue viruses, a group of four flaviviruses, are transmitted to man by Aedes aegypti.

Incidence of infectious mononucleosis at the Universities of California and Hawaii.

The observed rates of heterophil-positive infectious mononucleosis at the University of California at Davis and the University of Hawaii at Manoa were 1,212 and 37 per 100,000 students per academic year, respectively. The data collected suggest that the extraordinarily low incidence at the University of Hawaii may be due to the following factors: (1) underutilization of the student health service by students with infectious mononucleosis; (2) low proportion of Epstein-Barr virus-seronegative students; (3) high proportion of Asian students who appear to be less likely to develop heterophil-positive infectious mononucleosis; and (4) possible low efficiency in the transmission of primary Epstein-Barr virus infections.

In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody.

Five pairs of juvenile, dengue virus-susceptible rhesus monkeys were given normal or dengue-immune human cord-blood serum injected intravenously to a final dilution of 1:300. The pool of immune human cord-blood serum had a titer of antibody to dengue type 2 virus (D2V) of 1:140 in the plaque-reduction neutralization test and a titer of human monocyte infection enhancement of greater than 1:2,000,000. Fifteen minutes after inoculation of serum, animals were infected with D2V (strain no.

Absence of leukocytes permissive to dengue 2 virus in the acute phase of dengue hemorrhagic fever.

Patients with primary dengue infection developed dengue 2 virus (D2V) permissive peripheral blood leukocytes (PBL) 2--3 weeks after infection. PBL from healthy individuals with dengue antibody were permissive to D2V in vitro, suggesting that immunologically mediated in vitro D2V permissiveness persists for a relatively long time after recovery from dengue infection. However, PBL obtained from second infection dengue hemorrhagic fever patients did not support D2V growth during the acute phase of illness but did so during convalescence.

Effect of immune status on dengue 2 virus replication in cultured leukocytes from infants and children.

Cord blood leukocytes from neonates with maternal dengue antibody supported dengue 2 virus replication in vitro; those from neonates without maternal antibody did not. Cord bloods of infants born to dengue-immune mothers contained a potent enhancing factor which gradually decayed with age and which was absent from neonates born to nonimmune mothers. Permissiveness of cultures of washed peripheral blood leukocytes from infants with maternal antibody declined steadily with increasing age in parallel with the decay of maternal antibody, and the leukocytes were no longer permissive after 10 to 12 months.