Hantavirus pulmonary syndrome: an emerging infectious disease.
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Animals↗
Biomedical subjects
C J Peters
Publications and source records attributed to C J Peters.
Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness.
A mysterious respiratory illness with high mortality was recently reported in the southwestern United States. Serologic studies implicated the hantaviruses, rodent-borne RNA viruses usually associated elsewhere in the world with hemorrhagic fever with renal syndrome. A genetic detection assay amplified hantavirus-specific DNA fragments from RNA extracted from the tissues of patients and deer mice (Peromyscus maniculatus) caught at or near patient residences. Nucleotide sequence analysis revealed the associated virus to be a new hantavirus and provided a direct genetic link between infection in patients and rodents.
Animals↗
Hantavirus infection--southwestern United States: interim recommendations for risk reduction. Centers for Disease Control and Prevention.
This report provides interim recommendations for prevention and control of hantavirus infections associated with rodents in the southwestern United States. It is based on principles of rodent and infection control and contains specific recommendations for reducing rodent shelter and food sources in and around the home, recommendations for eliminating rodents inside the home and preventing them from entering the home, precautions for preventing hantavirus infection while rodent-contaminated areas are being cleaned up, prevention measures for persons who have occupational exposure to wild rodents, and precautions for campers and hikers.
Animals↗
Utilization of autopsy RNA for the synthesis of the nucleocapsid antigen of a newly recognized virus associated with hantavirus pulmonary syndrome.
A newly recognized hantavirus was recently found to be associated with an outbreak of acute respiratory illness in the southwestern United States. The disease, which has become known as hantavirus pulmonary syndrome, has an unusually high mortality (64%). Virus isolation attempts have been unsuccessful thus far, resulting in a lack of homologous antigen for use in diagnostic assays. For this reason, a molecular approach was initiated to produce recombinant homologous antigen. The virus nucleocapsid (N) protein was selected, since N has been shown to be a sensitive antigenic target in other hantavirus systems. The N protein open reading frame of the virus S genome segment was synthesized from frozen autopsy tissue by polymerase chain reaction amplification, followed by cloning and expression in Hela cells (vaccinia-T7 RNA polymerase system) and Escherichia coli. N protein-expressing Hela cells served as excellent antigens for an improved indirect immunofluorescence assay. Use of the E. coli-expressed N protein in an enzyme-linked immunosorbent assay improved the sensitivity and specificity when compared with heterologous antigens used previously. Preliminary analysis also indicates that the higher sensitivity could result in earlier detection of infected persons. These data demonstrate that even in the absence of a virus isolate, the necessary homologous antigen can be produced and can serve to improve the detection and diagnostic capabilities needed to combat this newly recognized fatal respiratory illness in the United States.
Amino Acid Sequence↗
Localization of Hantaan viral envelope glycoproteins by monoclonal antibodies in renal tissues from patients with Korean hemorrhagic fever H.
The role of viruses in several renal diseases is not documented clearly. The authors attempted to localize envelope glycoproteins of Hantaan virus in biopsy specimens from patients with Korean hemorrhagic fever (KHF) as evidence of direct viral invasion of renal tissues. The authors studied sequential sections of kidney biopsy specimens from 23 of 35 patients with serologically confirmed KHF diagnosed between June 1985 and December 1989. The sections were stained with the avidin-biotin-peroxidase complex method with monoclonal antibodies to G1 and G2 envelope glycoproteins. Control antibodies of the same isotype were used to rule out nonspecific staining, and hyperimmune rabbit sera or convalescent sera of patients with KHF were used for blocking tests. Normal renal tissues and kidney biopsy tissues from minimal-change nephrotic syndrome were used as negative control sections. The kidney biopsies were performed between the fifth and thirtieth days after onset of fever. The authors detected viral glycoproteins in renal tissues from 22 of the 23 patients. The viral glycoproteins were localized in the cytoplasm of the tubular epithelial cells, and the distribution of viral glycoproteins in the tubules was focal. Glycoproteins also were localized in the cytoplasm of the sloughed renal tubular epithelial cells, where tubular degenerative changes were prominent. These findings suggest the direct invasion of renal tubules by the virus and may partly explain the pathogenesis of acute renal failure in KHF.
Adolescent↗
Congenital lymphocytic choriomeningitis virus infection in twins.
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Animals↗
Lipopolysaccharide inhibits the production of lymphocytic choriomeningitis virus in a human monocytic cell line.
The human monocytic cell line THP-1 was used as a model to study the mechanism of infection in the monocyte/macrophage, a natural target of lymphocytic choriomeningitis virus (LCMV) infection in vivo. Both the virulent strain, LCMV.WE, and the avirulent strain, LCMV.ARM, infected THP-1 cells, but did not stimulate THP-1 cells to secrete interleukin 1 (IL-1) or tumour necrosis factor (TNF-alpha). When lipopolysaccharide (LPS) was added to THP-1 cells together with LCMV, an 80 to 90% reduction in the number of infected cells (measured by immunofluorescence) and a 90% reduction in viral plaques was observed 5 to 6 days post-infection. Neither interferon alpha (IFN-alpha) nor IFN-beta were detected in supernatants from THP-1 cells after the addition of LCMV, LPS, or LPS plus LCMV. In contrast, the same levels of IL-1 and TNF-alpha were observed in the presence of LPS and LCMV, or LPS alone. However, antibodies to IL-1, TNF-alpha, interleukin 6 and IFN-alpha did not block the antiviral effect of LPS. In kinetic studies, LPS added 1 day after adding LCMV to THP-1 cells was still effective in reducing the number of infected cells. Our findings suggest that LPS alters cellular metabolism, possibly through the induction of IFN-alpha, and that IFN-alpha in the absence of LPS suppresses virus production.
Cytokines↗
Pathogenesis of Pichinde virus infection in strain 13 guinea pigs: an immunocytochemical, virologic, and clinical chemistry study.
Pichinde virus has been adapted to produce lethal infection of Strain 13 guinea pigs. Viral replication and presence of viral antigen in frozen tissues stained by immunofluorescence has been previously described. Further investigation into the pathogenesis of this disease has been hampered by the lack of a light microscopic method for correlating histologic lesions and the presence of Pichinde viral antigens. For this purpose, we developed a sensitive immunocytochemical technique for staining Pichinde viral antigens in formalin-fixed, paraffin-embedded tissue. Enhancement of the immunocytochemical staining with nickel chloride markedly improved detection of viral antigens. We examined frozen and formalin-fixed tissues from Strain 13 guinea pigs for viral antigens by light microscopy and immunocytochemistry at various intervals after infection with Pichinde virus. Progressive involvement of different tissues correlated with organ injury measured by serum biochemical abnormalities. Pichinde viral antigen was first detected in splenic macrophages five days after infection and their subsequent destruction facilitated persistent viremia. The inability to clear virus led to multiple organ infection and vascular involvement. Ensuing infections involved particularly the liver, spleen, adrenal glands, lungs, and intestines. Gastroenteritis developed, with extensive involvement of the muscularis mucosa throughout the gastrointestinal tract. Water and food intake decreased rapidly after day 8, leading to marked weight loss. Fatty changes of the liver suggested metabolic derangement that was further exacerbated terminally by adrenal infection and pulmonary impairment.
Adrenal Glands↗
Field studies on the epidemiology of Venezuelan hemorrhagic fever: implication of the cotton rat Sigmodon alstoni as the probable rodent reservoir.
During February 1992, field studies on the epidemiology of Venezuelan hemorrhagic fever (VHF) were carried out in a rural area of Portuguesa State in central Venezuela. The objective of this work was to determine the prevalence of infection with Guanarito virus, the etiologic agent of VHF, among wild rodents and humans living within an endemic focus of the disease. A total of 234 rodents, representing nine different species, were collected and their spleens were cultured for virus. Thirty-one Guanarito virus isolates were made from two rodent species: 19 from 40 Sigmodon alstoni and 12 from 106 Zygodontomys brevicauda. Guanarito virus antibody rates among these two species were 5.1% and 15.0%, respectively. Nine of the 12 Z. brevicauda that yielded virus from their spleens also had Guanarito virus antibodies in their sera. In contrast, none of the 19 Guanarito virus-positive S. alstoni had antibodies to the virus. These data suggest that S. alstoni usually develops a persistent nonimmunizing infection with Guanarito virus, while Z. brevicauda develops an immunizing infection. Based on knowledge of the behavior of other human pathogenic arenaviruses, these results imply that S. alstoni is the principal rodent reservoir of Guanarito virus in nature. To determine the prevalence of Guanarito virus infection among humans in the same region, 195 people living near one of the rodent collecting sites were bled and their sera were tested for antibodies to the virus. Five individuals (2.6%) had Guanarito virus antibodies; all were adults, and two had been diagnosed previously as having VHF.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Changes in platelet-activating factor, catecholamine, and serotonin concentrations in brain, cerebrospinal fluid, and plasma of pichinde virus-infected guinea pigs.
Brain concentrations of platelet-activating factor (PAF), catecholamines, and serotonin were measured in control and Pichinde virus-infected strain 13 guinea pigs on postinoculation day (PID) 12. After virus inoculation, PAF concentrations increased 81% in cerebrum, 147% in diencephalon-brain stem, and 110% in cerebellum from baseline values of 2.6 +/- 0.3, 4.3 +/- 0.2, and 6.1 +/- 0.5 (ng/g wet tissue), respectively. Dopamine concentrations in the infected cerebrum and diencephalon-brain stem increased significantly, whereas norepinephrine concentration increased only in cerebrum. However, serotonin concentrations in all three regions of infected brain decreased significantly as compared with control values. There were no significant changes in epinephrine concentrations of infected brain. Norepinephrine and epinephrine concentrations in plasma and cerebrospinal fluid on PID 7 and 12 increased significantly as compared with control values, while plasma dopamine concentration increased significantly on PID 7. Increased brain PAF, dopamine, and and norepinephrine concentrations with decreased brain serotonin concentrations may mediate the hyperactivity of the hypothalamic-pituitary-adrenal axis and involve some unknown pathophysiologic processes of arenaviral infection. Furthermore, increased plasma catecholamine concentrations are associated with stress and may be partially responsible for the development of cardiovascular dysfunction and pulmonary edema during this viral disease.
Animals↗
Platelet-activating factor (PAF)-induced cardiopulmonary dysfunctions and their reversal with a PAF antagonist (BN 52021) in strain 13 guinea pigs.
Cardiovascular and respiratory responses to a 2 h intravenous constant infusion of PAF (5 and 10 ng/kg per min) were studied in strain 13 guinea pigs. PAF decreased arterial blood pressure, left systolic ventricular pressure, and cardiac output (CO). These cardiovascular changes were dose-dependent. The PAF-induced hypotension returned to a pre-infusion level spontaneously with increased total peripheral resistance despite continuous infusion of PAF. The decreased CO was most striking, and did not recover to pre-infusion levels due to depressed cardiac contractility and impaired ventricular relaxation. Respiratory responses to PAF infusion at these doses were mild and only occurred after serious cardiovascular dysfunctions developed. A higher dose of PAF (20 ng/kg per min) produced drastically decreased CO and dynamic lung compliance (Cdyn), increased pulmonary airway resistance, hypoventilation and apnea within 10-40 min. BN 52021, a PAF receptor antagonist, administered as a single i.v. dose (6 mg/kg) 15 min after PAF infusion, reversed most of cardiopulmonary dysfunctions and prevented death by increasing cardiac contractility, CO, and minute volume from extremely low values. The data suggest that marked cardiopulmonary disturbances induced by intravenous PAF infusion reflects certain pathophysiological mechanisms of diseases that may involve the cellular release of PAF. The administration of BN 52021 or other potent PAF antagonists may be beneficial under these circumstances.
Animals↗
Metabolism of platelet-activating factor in neutrophils isolated from Pichinde virus-infected guinea pigs.
Metabolism of platelet-activating factor (PAF) was studied in cultured polymorphonuclear neutrophils (PMNs) obtained from Pichinde virus-infected strain 13 guinea pigs. Neutrophils obtained from control and infected guinea pigs on postinoculation days 10 and 14 were incubated with [3H]lyso-PAF, [3H]PAF, or [3H]acetate. After incubation for 1 h at 37 degrees C, formation of [3H]acyl-PAF from either [3H]lyso-PAF or [3H]PAF increased significantly in PMNs from infected guinea pigs compared to control PMNs. Furthermore, total radioactivity from [3H]lyso-PAF or [3H]PAF was higher in PMNs from infected animals than in those from controls. However, compared to PAF production by control PMNs, production of PAF by infected PMNs was unchanged. These results suggest that PMNs may not be the major source of increased blood PAF levels during Pichinde viral disease.
Acetates↗
Venezuelan equine encephalitis-specific immunoglobulin responses: live attenuated TC-83 versus inactivated C-84 vaccine.
Venezuelan equine encephalitis (VEE)-specific immunoglobulin responses to the two vaccines, TC-83 (a live attenuated vaccine) and C-84 (a formalin inactivated vaccine derived from the TC-83 strain of virus) were evaluated using an antigen and isotype-specific enzyme-linked immunoadsorbent assay (ELISA). The VEE-specific ELISA for IgG, IgG subclasses, IgA and IgM were developed and standardized using sera from vaccine-exposed and unexposed human subjects. Paired human sera (before and 28 days after immunization) were tested from laboratory workers vaccinated with either TC-83 (Group A: 20 paired sera from subjects receiving a single TC-83 vaccine and with no prior history of vaccination) or C-84 in varying schedules (Group B: 19 paired sera from subjects who had a distant vaccination history to TC-83 but no evidence of neutralizing antibody; Group C: 19 paired sera from subjects receiving their first C-84 vaccination and no prior documented history of vaccination; Group D: 15 paired sera from subjects receiving a C-84 booster vaccination with prior history of C-84 but no TC-83 exposure). Sera were all tested for viral neutralization in vitro using a Vero cell monolayer for culturing virus and establishing 80% plaque reduction for each serum tested. All pre-sera tested demonstrated no plaque reduction neutralization at a level of 80% for a dilution of 1:10. ELISA antibody titers for all pre-sera with no prior VEE exposure through vaccination or possible environmental factors were negative at a titer of 1:160 for IgM, 1:80 for IgG, IgA, and G subclasses.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Infection of Macaca radiata with viruses of the tick-borne encephalitis group.
Our studies confirmed the susceptibility of Macaca radiata (bonnet macaques) to Kyasanur Forest disease (KFD) and enabled us to demonstrate KFD virus-specific gastrointestinal and lymphoid lesions. Significant histopathological changes occurred in the small and large intestine, spleen and lymph nodes; and viral antigens were found in these same organs by immunohistochemistry. Viral antigen-positive cells were always associated with histological evidence of necrosis, which suggests that cell death occurred directly from viral replication or secondarily from attack by immune mechanisms. In contrast, M. radiata infected with Omsk virus did not show any signs of clinical disease, and no virus could be isolated from tissues or blood at the end of the experiment. However, M. radiata infected with Russian spring-summer encephalitis (RSSE) developed clinical signs in the central nervous system; and, in one monkey, RSSE virus was isolated from the brain, and viral antigen was localized in neurons. Our data indicate that M. radiata is an excellent model to study human disease caused by KFD virus and could serve as a model for human disease caused by other, related strains of this group of viruses.
Animals↗
Enzyme immunosorbent assay for Ebola virus antigens in tissues of infected primates.
A sandwich enzyme immunosorbent assay (EIA) using a mixture of mouse monoclonal antibodies for antigen capture and polyclonal hyperimmune rabbit anti-Ebola virus serum for antigen detection was developed and evaluated on the tissues of monkeys naturally or experimentally infected with strains of Ebola viruses. When compared with virus isolation, the antigen detection EIA was both sensitive and specific: 44 of 45 (97.7%) liver homogenates and 38 of 41 (92.7%) spleen homogenates that were culture positive and tested by both techniques were positive for viral antigen, while 85 of 87 (97.7%) culture-negative liver homogenates and 66 of 66 culture-negative spleen homogenates were found to be antigen negative. The assay, initially developed to detect antigens of prototype African strains of Ebola virus, reliably detected related strains of Ebola virus found during two recent outbreaks of Ebola virus infection among imported, quarantined Macaca fascicularis monkeys in the United States. The assay allows economical and rapid testing of large numbers of tissue specimens. Antigen was found in homogenates of spleen and liver and in serum.
Animals↗
Aerosol infection of rhesus macaques with Junin virus.
The purpose of our work was to determine if aerosols of Junin virus can infect rhesus macaques and if the disease is the same as that produced by virus inoculated parenterally. The 6 macaques exposed to the virus by aerosol became acutely ill during the 3rd week after exposure, and all died. Three died by day 21, while the remainder died after 1 month. Junin virus was found primarily in visceral organs of those animals dying before 21 days after infection and in the central nervous system tissues from animals dying later. Histological changes were similar to those reported in rhesus monkeys after parenteral Junin viral infection. Gastrointestinal necrosis, however, was less severe in aerosol-infected animals and the associated septicemia was not seen. High levels of alpha interferon were detected by the 3rd day in all infected macaques. Experimental Argentine hemorrhagic fever induced by aerosol infection in rhesus macaques was similar to that seen after parenteral challenge and mimicked closely the clinical syndrome observed in humans.
Aerosols↗
Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.
Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.
Animals↗
Outbreak of fatal illness among captive macaques in the Philippines caused by an Ebola-related filovirus.
Following the detection of an Ebola-like virus in cynomolgus macaques recently imported into the United States from The Philippines, studies were initiated to document transmission at export facilities located in the latter country. At one export facility, 52.8% of 161 monkeys that died over a 2.5-month period were shown to be infected with this virus using an enzyme-linked immunosorbent assay to detect antigen in liver homogenates. A case fatality rate of 82.4% was documented for the infected monkeys. The initial anti-viral antibody prevalence among the captive macaques at this facility was 25.9% (indirect fluorescent antibody titer greater than or equal to 1:16). Followup documented infection of 24.4% of initially seronegative animals and 8.7% of initially seropositive monkeys. Being held in a gang cage versus a single cage was found to be a significant risk factor for subsequent virus infection, and the presence of IFA antibody was shown to predict protection. This study documents unequivocally for the first time the presence of an Ebola-related filovirus in Asia.
Animals↗