Showing papers on "Viremia published in 1987"

Clinical Virology of Lassa Fever in Hospitalized Patients

Abstract: We measured levels of virus in sequential specimens from 137 patients with Lassa fever. The probability of fatal disease increased significantly with the level of viremia measured either on admission or during the course of illness. The odds ratio of death in patients with viremia greater than 10 TCID50/ml was 3.7 (90% confidence interval, 1.9-7.2). The same ratio in patients with viremia greater than 10 TCID50/ml and with levels of aspartate aminotransferase greater than or equal to 150 IU/liter was 21.5 (95% confidence interval, 5.2-99.0). Virus was found in throat cultures from 39% of viremic patients, compared with 14% of nonviremic patients (P less than .002); however, the level of virus was usually less than or equal to TCID50/ml. Fewer than 3% of patients were viruric during acute illness, and virus was isolated from three of three samples of cerebrospinal fluid. On admission, 53% of patients had IgG antibodies, and 67% had IgM antibodies. Recovery was not associated with the presence of either IgG or IgM. Virus was isolated from greater than 100 serum specimens that also contained high titers of IgG. Clinical Lassa fever was shown to be a disseminated systemic, primary viral infection, with an outcome highly associated with viremia but not with development of antibody.

Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).

Abstract: Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection.

Abstract: Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.

Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes.

Abstract: Male and female BALB/c mice were inoculated with various concentrations of coxsackievirus, group B, type 3 (CVB3), ranging from 10 to 10(7) plaque-forming units (PFU) Lower viral doses (greater than 10(2) PFU) induced severe myocarditis in male mice but caused little injury in females With 10(7) PFU, females also developed severe disease Females may be relatively resistant to CVB3-induced myocarditis because virus entry into the blood and heart is less effective Males given 125I-CVB3 show approximately 2-4 and 20-fold more radioactivity in the peripheral blood and heart, respectively, than females No differences were observed between the sexes in 125I-bovine serum albumin penetration Sex steroid hormones influence viremia and virus localization; females given exogenous testosterone and progesterone demonstrate ten times more virus in their hearts than animals given estradiol The hormones may act by increasing virus receptor expression on endothelial cells and myocytes

Lack of attenuation of a candidate dengue 1 vaccine (45AZ5) in human volunteers.

Abstract: A dengue type 1, candidate live virus vaccine (45AZ5) was prepared by serial virus passage in fetal rhesus lung cells. Infected cells were treated with a mutagen, 5-azacytidine, to increase the likelihood of producing attenuated variants. The vaccine strain was selected by cloning virus that produced only small plaques in vitro and showed reduced replication at high temperatures (temperature sensitivity). Although other candidate live dengue virus vaccines selected for similar growth characteristics have been attenuated for humans, two recipients of the 45AZ5 virus developed unmodified acute dengue fever. Viremia was observed within 24 hr of inoculation and lasted 12 to 19 days. Virus isolates from the blood produced large plaques in cell culture and showed diminished temperature sensitivity. The 45AZ5 virus is unacceptable as a vaccine candidate. This experience points out the uncertain relationship between in vitro viral growth characteristics and virulence factors for humans.

Field and laboratory investigation of Crimean-Congo haemorrhagic fever virus (Nairovirus, family Bunyaviridae) infection in birds.

Abstract: In November 1984 a case of Crimean-Congo haemorrhagic fever (CCHF) occurred in a worker who became ill after slaughtering ostriches (Struthio camelus) on a farm near Oudtshoorn in the Cape province of South Africa. The diagnosis was confirmed by isolation of CCHF virus from the patient's serum and by demonstration of a specific antibody response. It was suspected that infection was acquired either by contact with ostrich blood or by inadvertantly crushing infected Hyalomma ticks while skinning ostriches. Reversed passive haemagglutination-inhibition antibody to CCHF virus was detected in the sera of 2292 ostriches from farms in Oudtshoorn district, including 69 from the farm where the patient worked, but not in the sera of 460 birds of 37 other species. In pathogenicity studies domestic chickens proved refractory to CCHF infection, but viraemia of low intensity (maximum titre 2.5 log10 mouse ic LD50/ml) followed by a transient antibody response occurred in blue-helmeted guinea fowl (Numidia meleagris). These results offer the first direct evidence that some bird species are susceptible to CCHF virus infection.

Horizontal transmission of murine retroviruses.

Abstract: Both a feral mouse ecotropic virus (WM-E) and Friend ecotropic virus (F-MuLV) were transmitted horizontally among adult mice. Infection resulted in the production of antiviral antibody in the recipients, with no evidence of viremia or clinical disease. However, persistent low-level virus replication was detectable in the spleens of these mice as long as 8 months after initial infection. External secretions, including saliva, semen, and uterine secretions from viremic mice contained high concentrations of infectious virus. Nevertheless, transmission occurred only from viremic males to either males or females. Male-to-male transmission appeared to occur by parenteral inoculation of infectious saliva during fighting behavior. Evidence is presented that infection of females was by the venereal route. Of four mouse strains examined, NFS/N, IRW, and C57L females were all susceptible to venereal infection, whereas AKR mice were not. Since AKR mice are susceptible to infection by WM-E administered parenterally, this resistance appeared to be mediated by local viral interference due to the high-level expression of endogenous Akv gp70 within the female reproductive tract. Although both WM-E and F-MuLV were transmitted from viremic males to females, infection by WM-E was significantly more efficient than that by F-MuLV. This difference correlated with a distinct difference in cellular tropism of WM-E and F-MuLV within the epididymis of viremic males. F-MuLV gp70 was expressed only within stromal elements, whereas WM-E gp70 was seen largely within the epithelial lining cells and luminal contents of the duct. No evidence of virus expression within germ cells was observed. The possible influence of virus expression by epithelial cells of the female reproductive tract on infection of embryos is discussed.

Natural History of Endemic Type D Retrovirus Infection and Acquired Immune Deficiency Syndrome in Group-Housed Rhesus Monkeys

Abstract: A 2.5-year epidemiologic study of a breeding group of rhesus monkeys (Macaca mulatta), which is a focus of endemic simian acquired immunodeficiency syndrome (SAIDS), demonstrated a strong association between the occurrence of SAIDS and infection with a type D retrovirus, SAIDS retrovirus serotype 1 (SRV-1). Of 23 healthy "tracer" juvenile rhesus monkeys, 19 (83%) died with SAIDS within 9 months of introduction into the resident SAIDS-endemic population. In contrast, 21 healthy "sentinel" juvenile rhesus monkeys placed in the same outdoor enclosure but denied physical contact with the SAIDS-affected group by a 10-foot-wide "buffer zone" remained free of SRV-1, SRV-1 antibody, and disease for 2.5 years. The SAIDS-specific mortality rate was significantly higher in juveniles than in adults. In repeated serologic testing, the overall prevalence of SRV-1 antibody ranged from 68 to 85%. Antibody prevalence increased with age. Seroconversion was found to be a poor indicator of infection rate, as approximately 50% of virus-positive juvenile monkeys had no antibody detectable by enzyme-linked immunosorbent assay. Repeated viral isolations from all animals revealed 1) SRV-1 viremia with clinical SAIDS; 2) persistent viremia and viral shedding in apparently healthy animals; 3) transient viremia and clinical recovery; 4) intermittent viremia, suggesting activation of latent infections; and 5) viremia in a 1-day-old infant, suggesting transplacental transmission. The prevalence of SRV-1 antibody in SAIDS-free breeding groups of rhesus monkeys was 4%. The seroprevalence of antibodies against human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), and simian immunodeficiency virus (SIV; formerly STLV-III) was uniformly low or absent in both SAIDS-free and SAIDS-affected groups of rhesus monkeys, demonstrating that these retroviruses are not etiologically linked to SAIDS at the California Primate Research Center.

Virus-specific factors in experimental Argentine hemorrhagic fever in rhesus macaques.

Abstract: A nonhuman primate model for Argentine hemorrhagic fever has been developed that closely mimics the human clinical syndrome. Parenteral infection of adult Macaca mulatta with low-passage isolates of two Junin viral strains resulted in distinctive hemorrhagic or neurological disease in rhesus macaques that correlated with clinical illness patterns present in the humans from whom the viral strains were obtained. Transient leukopenia, together with thrombocytopenia and secondary bacterial septicemia, were documented among animals infected with both viral strains. In contrast, differing patterns of viremia, oropharyngeal viral shedding, and antibody response occurred in the two virus-infected groups. These results, together with postmortem virologic and histopathologic findings, suggest that viral-strain-specific factors are important determinants of clinical disease patterns in this model system.

Humoral immune response of calves to bluetongue virus infection.

Abstract: Humoral immune responses of 7 calves to bluetongue virus (BTV) infection were evaluated by plaque-reduction assay and immunoblotting. Most readily interpretable results were obtained with the immunoblot assay when colostrum-deprived calves were used, and sera were reacted with proteins in partially purified extracts of BTV. Viremia persisted in calves for 35 to 56 days, and BTV coexisted in blood for several weeks with virus-specific neutralizing antibody. Calves developed antibody to virus protein 2, the major determinant of virus neutralization, at 14 to 28 days after inoculation; this time interval also coincided with the appearance of neutralizing antibody in serum. Virus clearance in BTV-infected calves did not coincide with humoral immune responses to protein 2 or other virion proteins.

Protection of Junín virus-infected marmosets by passive administration of immune serum: association with late neurologic signs.

Abstract: Argentine hemorrhagic fever (Junin virus) is a human viral disease for which immune therapy proves effective, though a late neurologic syndrome is occasionally associated with the treatment We attempted to determine in the infected marmoset Cullithrix jacchus whether immune therapy leads to protection and/or CNS damage Fifteen C jacchus were inoculated with 103 tissue culture infectious dose 50% (TCID50) of the XJ strain of Junin virus On day 6 post infection (pi), 12 primates were treated with homologous immune serum Animals were observed daily; and hematologic, serologic, virologic, and histologic studies were performed All primates, both treated and controls, presented leukopenia, thrombocytopenia, anemia, and weight loss from day 14 pi onward The three control animals died on days 22, 25, and 32 pi Among the 12 treated monkeys, 3 died on days 21, 22, and 29 Hematologic values returned to normal during the second month; initial weight was recovered by the fourth month Three out of the nine survivors showed neurologic alterations of various degrees, with hind-limb paralysis in the most severe case Among treated monkeys, viremia and viral titers in the lungs, kidney, and lymph nodes were lower than in controls Neutralizing antibodies were present in high titers in all treated marmosets, except in the one presenting paralysis in which values were minimal and viral persistence was detected in CNS In conclusion, immune serum treatment of Junin virus-infected marmosets was found to reduce mortality from 100% to 25% Viremia and viral titers in organs were lowered, and late neurologic signs appeared in 30% of treated survivors

Viremia and immune response with sequential phlebovirus infections.

Abstract: Four groups of hamsters were infected sequentially with various combinations of Arumowot, Chagres, and Gabek Forest viruses. Following each infection, the survival, level of viremia, and immune response of the animals were monitored. All of the agents produced viremia in the hamsters, regardless of the order of their administration. The antibody response, as measured by plaque reduction neutralization test, was monotypic even after two consecutive phlebovirus infections. Arumowot and Chagres viruses produced nonfatal infections in adult hamsters, which were characterized by viremia of several days duration and subsequent antibody formation. In contrast, Gabek Forest virus produced a fulminating and rapidly fatal disease in phlebovirus nonimmune animals. In hamsters previously infected with Chagres and/or Arumowot viruses, Gabek Forest infection was less severe, indicating some degree of cross-protection. The degree of cross-protection was in part related to the sequence of previous phlebovirus infections. No evidence of immune enhancement or other immunopathologic events were observed in the animals.

Identification of the bovine leukemia virus transactivating protein (p34x).

Abstract: Enzootic bovine leukosis (EBL) has been recognized as a neoplasm of infectious origin for half a century. The agent, bovine leukemia virus (BLV), is a retrovirus discovered in 1969 in short-term cultures of peripheral lymphocytes from animals with persistent lymphocytosis, a benign response to BLV infection. A virus distantly related to BLV was more recently identified as the etiological agent in the vast majority of cases of adult T cell leukemia and named for that reason human T-lymphotropic virus I (HTLV-I) [20]. The pathologies of BLV- and HTLV-I-in-duced diseases are notably similar, namely absence of chronic viremia, a long latency period, and lack of preferred integration sites in tumors. A second human virus, called HTLV-II, was identified in the Mo T cell line, derived in 1976 from the spleen of a patient with T cell-variant hairy cell leukemia [2, 10]. Other isolates of HTLV-I and -II have since been obtained around the world. Both viruses not only transform normal T-lymphocytes but might also very well be involved in a number of degenerative diseases of the nervous system.

Characterization of Equine Infectious Anemia Virus Variants Generated in Vivo and in Vitro and a Rapid Assay for Virus-Specific Antibody.

Abstract: Three Shetland ponies (A, B and C) were inoculated with plasma from a pony with clinical signs of equine infectious anemia (EIA) and observed for 165 to 440 days. Clinical signs of EIA marked by high fever ( 39.5°C) lasting 2-4 days were observed 2-3 weeks after infection and one to four such episodes occurred in each pony. EIAV was reisolated from plasma by end-point dilution in fetal equine kidney (FEK) cells and a plasma viremia 103-5 TCID50/ml was observed during each episode. A total of seven virus isolates were recovered. Cross-neutralization tests with sequential serum samples showed that the four viruses isolated from pony A during febrile episodes 4-5 weeks apart were serologically different. Tryptic peptide map analysis of these isolates revealed additions or deletions between each isolate and its immediate predecessor. .Western blot analysis of these four isolates including those from ponies B and C with a panel of monoclonal antibodies confirmed antigenic variation in both gp90 and gp45. Both conserved and variable epitopes were identified in each glycoprotein with greatest variation in gp90. Analysis with MAbs confirmed similar antigenic variation in an in vitro variant generated in cell culture. The humoral response to EIAV was monitored for anti-virus antibodies by AGID, Western blots and a novel single-step immunoblot devised in this study for rapid assay of EIAV antibodies and antigens. Specific IgG directed against determinants of EIAV gp90, gp45 and p26 in homologous and heterologous virus isolates was detectable within one month after infection. The group-specific determinants in gp90 and gp45 were more antigenic than those in p26. Neutralizing antibodies first detectable within two months were observed to be effective only to viruses isolated prior to serum collection but became broadly reactive later in the infection regardless of the number of clinical episodes. Our data showed that rapid antigenic variation occurred during persistent infection with EIAV in ponies and in cell culture in the presence of immune serum, and neutralizing antibody response broadened during the course of EIA. The conserved antigenic determinants of EIAV gp90 and gp45 identified in this and previous studies will be useful in diagnostic procedures and may have potential for vaccines against EIA.