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At least 19 recordsLinked to original sources
PubMed2006

Association of transforming growth factor-beta 1 functional polymorphisms with natural clearance of hepatitis C virus.

Transforming growth factor (TGF)-beta 1 suppresses the proliferation and cytotoxicity of natural killer (NK) cells, which play critical roles in resolving hepatitis C virus (HCV) infection, especially during the acute phase. We examined 230 anti-HCV antibody-positive subjects for HCV RNA and the -509T/C genotype in the TGF-beta 1 gene promoter. The -509CC genotype and the -509C allele were significantly associated with higher HCV clearance rates (P=.01) and with lower transcriptional activity. The genetic effect remained significant even after adjustment for a history of transfusion. Low TGF- beta 1 producers might have less suppression of NK cells and be more likely to resolve HCV infection.

Adult↗
PubMed2004

An analysis of tumor necrosis factor alpha gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection.

The cytokine tumor necrosis factor alpha (TNF-alpha) is important in generating an immune response against a hepatitis C virus (HCV) infection. The functions of TNF-alpha may be altered by single-nucleotide polymorphisms (SNPs) in its gene, TNF. We hypothesized that SNPs in TNF may be important in determining the outcome of an HCV infection. To test this hypothesis, we typed nine TNF SNPs in a cohort of individuals with well-defined HCV outcomes. Three of these SNPs were typed in a second cohort. Data were analyzed using logistic regression stratifying by ethnicity, since rates of HCV clearance differ in black subjects versus white subjects. The SNP -863A was associated with viral clearance in black subjects (odds ratios (OR) 0.52, 95% confidence interval (CI) 0.29-0.93). Furthermore, the common wild-type haplotype -863C/-308G was associated with viral persistence in black subjects (OR 1.91, 95% CI 1.24-2.95). These findings were independent of linkage with human leukocyte antigen (HLA) alleles. Further study of this polymorphism and haplotype is needed to understand these associations and the role of TNF-alpha in determining outcomes of HCV infection.

Black or African American↗
PubMed1997

Role of gamma interferon in natural clearance of Bordetella pertussis infection.

Using a mouse model of Bordetella pertussis infection, we have analyzed the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of infection 6 to 8 weeks postinfection. In contrast, neither adult SCID mice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and both strains died within 3 to 5 weeks postinfection. Short-term T-cell lines generated from the draining lymph nodes of the lungs of infected BALB/c mice were found to be CD4+ and produced IFN-gamma but no detectable interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c and C57BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week postinfection and then subsequently declined. Further exploration of a potential role for IFN-gamma demonstrated that infection of adult BALB/c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal antibodies resulted in greater numbers of bacteria recovered from the lungs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection. Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertussis infection.

Animals↗
PubMed1989

In vivo clearance of natural and modified surfactant.

The loss of radiolabelled phosphatidylcholine associated with surfactants and lipid extracts of surfactants from different species sources was measured following tracheal injection into the lungs of adult and 3 day old rabbits. Clearance was more rapid from the lungs of adult than 3 day old rabbits. The percent labelled phosphatidylcholine cleared per 24 h did not change independently of dose injected indicating that clearance and catabolic pathways were not saturable in either group of rabbits. Different species sources or lipid extraction of natural surfactants did not alter clearance rates very much in the 3 day old rabbits. Small differences in clearance rates were identified by comparing rabbit surfactant with calf surfactant or Surfactant-TA in the adult rabbits. These results indicate that the lungs of developing and adult rabbits can clear large doses of surfactants from multiple sources at rates comparable to the species common natural surfactant.

Animals↗
PubMed2002

Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0.66; p<0.05). Fasting blood glucose levels were significantly correlated to serum alanine levels (r=0.70; p<0.05). Although Homa-R was significantly correlated to BMI in active patients (r=0.74 p<0.05), it was not correlated to amino acid levels. In conclusion, the results of the current study demonstrate that patients with CD have significant changes in serum and urinary concentration of several amino acids and changes in renal clearance of some specific amino acids. Normalization of cortisol levels restored the amino acid profile.

Adult↗
PubMed1986

Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species.

Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 +/- 1.8% per 24 h (mean +/- SE) of the injected doses of surfactant that contained from 0.41 to 10.2 mumol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.

Animals↗
PubMed2000

Clearance of anti-double-stranded DNA antibodies: the natural immune complex clearance mechanism.

OBJECTIVE: To develop an in vitro model for investigating the mechanism by which autoantibodies in immune complexes (ICs) that are bound to primate erythrocytes via antigen-based heteropolymers (AHPs) are cleared from the circulation and localized to the liver. METHODS: IgG anti-double-stranded DNA (anti-dsDNA) antibodies in ICs with dsDNA were bound to human erythrocytes via complement receptor 1 (CR1) either by opsonization with normal human serum as a complement source or through the use of an AHP, which consists of an anti-CR1 monoclonal antibody (mAb) that is chemically crosslinked with dsDNA. We performed parallel investigations of the mechanism of transfer of both types of erythrocyte-bound ICs to a monocytic cell line (U937). Erythrocytes with CR1-bound ICs were incubated with U937 cells under a variety of conditions, and subsequently, the levels of IgG anti-dsDNA, CR1, AHP, or C3b on both erythrocytes and U937 cells were measured by flow cytometry with appropriate fluorescently labeled probes. RESULTS: In the presence of U937 cells, both the AHP-anti-dsDNA and C3b-opsonized ICs were rapidly removed from the erythrocytes; at 37 degrees C, more than half of the complexes were removed in 2 minutes. Monomeric mouse IgG2a mAb blocked the transfer of both types of complexes by 75%, suggesting that Fcgamma receptor type I (FcgammaRI) is the main phagocyte receptor responsible for the removal of ICs from erythrocytes. Levels of CR1 on the erythrocyte surface were reduced during transfer of the AHP-anti-dsDNA ICs, suggesting that transfer involves a concomitant removal of CR1, presumably by proteolysis. CONCLUSION: Transfer of AHP-anti-dsDNA ICs from erythrocyte CR1 to model phagocytes occurs by a mechanism that is similar to the natural mechanism of IC clearance, involving recognition by FcgammaRI and removal of erythrocyte CR1 as key steps.

Animals↗
PubMed1984

Russell's viper venom levels in serum of snake bite victims in Burma.

Serum levels of venom antigen were measured using enzyme-linked immunosorbent assay (ELISA) in 38 Russel's viper bite victims before and after administration of 40 ml of monovalent liquid antivenom. Initial serum levels ranged from one with less than 10.0 ng to 290 ng/ml and in one case a level of 75 ng/ml was detected 27 hours after the bite. Serum venom levels after liquid monospecific antivenom therapy indicated that venom clearance was similar in each case to the natural clearance of venom in the absence of antivenom therapy. In one case a venom level of 11.5 ng/ml was detected 66 hours after liquid antivenom therapy whereas in two fatal cases, serum venom levels of 95 ng/ml and 185 ng/ml were detected after the same interval. Failure of complete neutralization of venom is probably the result of loss of potency of antivenom during improper storage. The amount of venom excreted in the urine was not related to initial serum levels.

Adolescent↗
PubMedDate not supplied

Evaluation of plasmapheresis in the treatment of an acute overdose of carbamazepine.

OBJECTIVE: To report the use of plasmapheresis in the treatment of an acute overdose of carbamazepine. CASE SUMMARY: A 21-year-old black man was admitted unresponsive and combative following a carbamazepine overdose. The total body load of carbamazepine was approximated at 5.91 g using an assumed volume of distribution of 1.4 L/kg. The patient underwent three plasmapheresis treatments. A total of only 335.82 mg of carbamazepine was removed by this process. DISCUSSION: Case reports in the literature were reviewed and compared. Carbamazepine concentrations lack correlation with the clinical outcome. Our patient's symptoms were consistent with the Weaver classification system. Carbamazepine clearance increased by almost 70 percent above its natural clearance during plasmapheresis. However, a significant rebound effect was observed after plasmapheresis: 40.1 percent after the first and 18.3 percent after the second treatment. CONCLUSIONS: Plasmapheresis did not seem to have a great impact on the patient's clinical status. Under the circumstances we find it extremely difficult to recommend plasmapheresis in the treatment of an acute overdose of carbamazepine.

Adult↗
PubMed2001

[Prognosis of chronic hepatitis C with regard to the aim of treatment].

Epidemiology of hepatitis C virus(HCV) infection and clinical prognosis of chronic hepatitis C were presented here to reveal the object of treatment of Chronic Hepatitis C. Hepatitis C Virus is transmitted by blood and blood products. After acute HCV infection, about 70% developed persistent HCV infection, and the diagnosis is by finding viral RNA in the serum of patients with anti-HCV antibody. Persistent HCV infection causes chronic hepatitis, in which the natural clearance of HCV is almost impossible and there is almost no natural cure for chronic hepatitis caused by HCV. Chronic hepatitis C tends to develop gradually and to progress to liver cirrhosis, and is involved in the pathogenesis of hepatocellular carcinoma. In Japanese patients with chronic hepatitis C, 45% developed liver cirrhosis pass through a phase of chronic active hepatitis over a 15-year course after initial HCV infection, and 25% developed hepatocellular carcinoma over a 20-year course after the initial HCV infection. In addition the remaining patients may start to develop rapidly to chronic active hepatitis and to liver cirrhosis after 20 to 30 years duration of inactive phase. Thus, this type of chronic hepatitis reveals a poor long-term prognosis. For etiological treatment of chronic hepatitis C, eradication of persistent HCV infection is needed. If this is impossible, then preventing the development of liver cirrhosis and hepatocellular carcinoma is important.

Antiviral Agents↗
PubMed1991

Clearance of neonatal antiHBc following hepatitis B vaccination: relationship to antiHBs levels.

The persistence of antiHBc following hepatitis B virus (HBV) infection is sometimes regarded as evidence of a past infection, and the antiHBc inhibition of T-cell cytotoxic killing of HBV may be one way of tolerance leading to the carrier state. A model for studying the possibility of an immune tolerance occurring in the human situation was to observe the natural clearance rate of total antiHBc in babies who have acquired naturally maternal transferred antibodies, and to compare antiHBcIgG clearance and development of hepatitis B surface antigenaemia with the level of antibody to HBsAg (antiHBs), which is normally known to be virucidal. Two hundred and ninety-one normal infants who received hepatitis B vaccination in 1984 were followed and studied at six months, one, two and four years. AntiHBc was not found in any control infants born of HBsAg negative mothers. One child became antiHBc positive at four years reflecting acquired infection when antiHBs level had fallen to 36 mIU per ml. AntiHBc cleared in 66% of HBsAg pos./'e' neg. children at one year and completely by two years. In contrast, antiHBc clearance in children born of HBsAg pos./'e' pos. was inversely related to the antiHBs levels. Those with antiHBs levels over 50 mIU per ml cleared antiHBc more rapidly and were HBsAg negative, whereas in 28/49 (57%) HBs antigenaemia were associated more often with antiHBs under 10 mIU per ml and in 2/43 (5%) at levels between 11 to 50 mIU per ml. Two children who had later developed HBs antigenaemia in the presence of antiHBs after responding to earlier passive-active immunisation, suggest either defective antiHBs and/or the development of mutants or variants.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed2005

Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.

BACKGROUND: Neutrophil apoptosis and phagocytic clearance have been proposed as key determinants affecting the resolution of airway inflammation. Objective To determine the kinetics of neutrophil priming, recruitment, activation and subsequent clearance in a naturally occurring equine disease model of neutrophilic pulmonary inflammation. METHODS AND RESULTS: A 5 h mouldy hay/straw challenge in hypersensitive horses induced transient pulmonary dysfunction lasting 4 days. At 24 h circulating neutrophils were primed and displayed delayed rates of spontaneous apoptosis in vitro. Neutrophil numbers in the airspaces peaked at 5 h and then fell abruptly, returning to pre-challenge levels by 4 days. Airspace neutrophils demonstrated increased respiratory burst activity compared with circulating cells and equine neutrophil elastase 2A concentrations increased in parallel with neutrophil numbers indicating in vivo priming and degranulation. The number of apoptotic neutrophils and proportion of alveolar macrophages containing phagocytosed apoptotic neutrophils increased significantly at 24 h and 4 days post-challenge corresponding to the period of most rapid neutrophil clearance. CONCLUSION: This is the first demonstration of spontaneous neutrophil apoptosis and phagocytic removal in a natural disease model of airway inflammation and provides critical kinetic data to support the hypothesis that this clearance pathway plays a central role in the resolution of neutrophilic inflammation.

Allergens↗
PubMed1995

Clearance pathways of soluble immune complexes in the pig. Insights into the adaptive nature of antigen clearance in humans.

Efficient delivery of immune complexes (ICs) to the mononuclear phagocytic system, and subsequent IC processing, may prevent their potentially harmful effects in other tissues and may also be important in the development of humoral immune responses. In mice, rabbits, and primates, the liver and spleen are the main sites of IC clearance. It has been demonstrated previously that the pulmonary capillaries in the pig are lined with macrophages and that certain particulates, including bacteria, localize to this organ. In this study, we used gamma scintigraphy to explore the sites and kinetics of clearance of soluble IC comprising 123I-labeled hepatitis B surface Ag (HBsAg):porcine anti-HBsAg in the Large White pig. At t = 10 min after i.v. injection, 43 +/- 5% (mean +/- SE) IC localized in the lungs, and 36 +/- 6% counts in the liver. At t = 85 min, values were: lungs, 15 +/- 4% and liver, 29 +/- 2%. Findings were similar following intraarterial injection. Complement depletion resulted in more rapid initial IC clearance (t1/2 = 5 min), reduced lung uptake (23 +/- 3% at 10 min), and impaired IC catabolism. In normal animals, 5 to 7% injected IC bound to PBMCs, but no E binding was seen. A fall in PBMC numbers (46 to 59% of baseline), was observed following IC injection. These findings contrast with our previous observations using analogous IC in humans, in which we did not observe any change in peripheral blood leukocyte counts consequent upon complex processing, suggesting that in humans, Es may function as a buffering system for complement-bearing IC in the circulation, preventing their interaction with leukocytes bearing complement and FcR, and the potential activation of these cells.

Animals↗
PubMed1999

Translating ribosomes inhibit poliovirus negative-strand RNA synthesis.

Poliovirus has a single-stranded RNA genome of positive polarity that serves two essential functions at the start of the viral replication cycle in infected cells. First, it is translated to synthesize viral proteins and, second, it is copied by the viral polymerase to synthesize negative-strand RNA. We investigated these two reactions by using HeLa S10 in vitro translation-RNA replication reactions. Preinitiation RNA replication complexes were isolated from these reactions and then used to measure the sequential synthesis of negative- and positive-strand RNAs in the presence of different protein synthesis inhibitors. Puromycin was found to stimulate RNA replication overall. In contrast, RNA replication was inhibited by diphtheria toxin, cycloheximide, anisomycin, and ricin A chain. Dose-response experiments showed that precisely the same concentration of a specific drug was required to inhibit protein synthesis and to either stimulate or inhibit RNA replication. This suggested that the ability of these drugs to affect RNA replication was linked to their ability to alter the normal clearance of translating ribosomes from the input viral RNA. Consistent with this idea was the finding that the protein synthesis inhibitors had no measurable effect on positive-strand synthesis in normal RNA replication complexes. In marked contrast, negative-strand synthesis was stimulated by puromycin and was inhibited by cycloheximide. Puromycin causes polypeptide chain termination and induces the dissociation of polyribosomes from mRNA. Cycloheximide and other inhibitors of polypeptide chain elongation "freeze" ribosomes on mRNA and prevent the normal clearance of ribosomes from viral RNA templates. Therefore, it appears that the poliovirus polymerase was not able to dislodge translating ribosomes from viral RNA templates and mediate the switch from translation to negative-strand synthesis. Instead, the initiation of negative-strand synthesis appears to be coordinately regulated with the natural clearance of translating ribosomes to avoid the dilemma of ribosome-polymerase collisions.

Anisomycin↗
PubMed1997

Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle.

The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF. In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA) conjugate, depolymerized alginate (3064) TA conjugate (D-ALG TA), or P. aeruginosa alginate (6680 + 8839). The vaccines could, however, not improve the very efficient natural clearance of P. aeruginosa from the lungs of the rats. In a rat model of chronic P. aeruginosa lung infection we found that none of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. This response was achieved within the first week after challenge in D-ALG TA immunized rats; in the controls, the inflammation was still acute 4 weeks after challenge. Rats immunized with D-ALG TA had a significantly reduced severity of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders. The mortality due to the infection was significantly lower in C3H/HeN mice compared to Balb/c mice (p < 0.0003). P. aerurinosa was cleared more efficiently by C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology than Balb/c mice (p < 0.025). Supernatants from Concanavalin A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis.

Animals↗
PubMed2005

Phenytoin intoxication in critically ill patients.

Phenytoin intoxication can result in major and possibly life-threatening disorders. Furthermore, the hepatic clearance can become saturated, thus, shifting the elimination from first- to zero-order kinetics. This results in a slow elimination of the compound in case of intoxication. The treatment modalities for phenytoin overdose are limited. Taking into account the high level of protein binding, the molecule is not easily eliminated from the body by means of extracorporal epuration. Although reports exist on the use of MARS (molecular adsorbents recirculating system) dialysis, peritoneal dialysis, and standard dialysis for the elimination, in practice, hemoperfusion, is the most often applied technique. The authors report the case of a hypoalbuminemic patient with severe neurologic signs of phenytoin intoxication (total concentration moderately elevated, free fraction high). A combination of high-flux dialysis and hemoperfusion resulted in a considerable extraction of the drug, accelerating the natural clearance from the body and ameliorating clinical signs of intoxication. In selected patients (with a high free fraction of phenytoin), high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion.

Epilepsy↗
PubMed1996

Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice.

Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815 mastocytoma cells. The effect of histamine was apparently mediated by H2-type histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist. Histamine did not affect clearance of tumour cells in animals depleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in vivo. None of these lymphokines significantly affected the clearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2R antagonism rather than non-specific toxicity. It is concluded that histaminergic mechanisms may be involved in the regulation of NK cell function in vivo.

Animals↗
PubMed2003

Clearance of a productive lentivirus infection in calves experimentally inoculated with caprine arthritis-encephalitis virus.

Lentiviruses have long been considered host-specific pathogens, but several recent observations demonstrated their capacity to conquer new hosts from different species, genera, and families. From these cross-species infections emerged new animal and human infectious diseases. The successful colonization and adaptation of a lentivirus to a nonnatural host depends on unspecific and specific host barriers. Some of those barriers exert a relative control of viral replication (i.e., cytotoxic T-lymphocyte response, viral inhibitory factors), but none of them was found able to totally clear the infection once the retrovirus is fully adapted in its host. In this study we examined the evolution of the host-lentivirus interactions occurring in an experimental animal model of cross-species infection in order to analyze the efficiency of those barriers in preventing the establishment of a persistent infection. Five newborn calves were inoculated with caprine arthritis-encephalitis virus (CAEV), and the evolution of infection was studied for more than 12 months. All the animals seroconverted in the first 0.75 to 1 month following the inoculation and remained seropositive for the remaining time of the experiment. Viral infection was productive during 4 months with isolation of replication competent virus from the blood cells and organs of the early euthanized animals. After 4 months of infection, neither replication-competent virus nor virus genome could be detected in blood cells or in the classical target organs, even after an experimental immunosuppression. No evidence of in vitro restriction of CAEV replication was observed in cells from tissues explanted from organs of these calves. These data provide the demonstration of a natural clearance of lentivirus infection following experimental inoculation of a nonnatural host, enabling perspectives of development of new potential vaccine strategies to fight against lentivirus infections.

Animals↗