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[Graft immunity in lung transplantation].

INTRODUCTION: Lung transplantation is an effective treatment for end-stage respiratory failure, however immunological mismatch poses a major threat to graft function. STATE OF THE ART: An inflammatory process within the lung is initiated at the time of brain death of the donor which, even in the absence of rejection or infection, persists in the recipient after transplantation. Although immuno-suppressive therapy is able to control the cellular immune response, alveolar macrophages remain in an activated state and interactions between T cells and epithelial cells continue. Acute rejection is triggered by T cell activation with an amplification of the inflammatory process associated with mononuclear cells infiltration. The major complication of pulmonary transplantation is bronchiolitis obliterans, a pan-bronchitic process due in part to a chronic rejection process arising from the interactions between epithelial and immune cells. This immune process results in progressive tissue remodelling. Viral infections may influence pulmonary transplantation by interacting directly with the immune system; infections due to cytomegalovirus and common respiratory viruses may play a role in the long term decline of graft pulmonary function. PERSPECTIVES: Concepts in lung transplantation immunology will evolve in forth-coming years as induction of microchimerism in the recipient is developed and/or organs from genetically modified porcine donors become available. CONCLUSION: Improvements in immunosuppressive regimens are needed to reduce the risk of bronchiolitis obliterans in the transplanted lung.

Acute Disease↗

Combined antiviral-antimediator treatment for the common cold.

A randomized, controlled, double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds. In all, 150 healthy men and women (aged 18-51 years) were randomly assigned to 1 of 3 groups: intranasal interferon (IFN)-alpha2b (6 x 10(6) U every 12 h x 3) plus oral chlorpheniramine (12 mg extended release) and ibuprofen (400 mg) every 12 h for 4.5 days (n=59 subjects); intranasal placebo plus oral chlorpheniramine and ibuprofen (n=61 subjects); or intranasal and oral placebos (n=30 subjects). Treatment was started 24 h after intranasal viral challenge. During the 4.5 days of treatment with IFN-alpha2b, chlorpheniramine, and ibuprofen, the daily mean total symptom score was reduced by 33%-73%, compared with placebo. Treatment reduced the severity of rhinorrhea, sneezing, nasal obstruction, sore throat, cough, and headache and reduced nasal mucus production, nasal tissue use, and virus concentrations in nasal secretions. IFN-alpha2b added to the effectiveness of chlorpheniramine and ibuprofen and was well tolerated.

Adolescent↗

Characterization of the T cell response to human rhinovirus in children: implications for understanding the immunopathology of the common cold.

Human rhinovirus (HRV) is a frequent respiratory pathogen, responsible for a large proportion of cases of the "common cold" and linked to acute asthma, especially in children. T cell responses to HRV and their contribution to HRV-associated pathology were investigated. T cells were obtained from tonsils removed from children at routine tonsillectomy. Proliferative and cytokine responses were measured after in vitro restimulation with purified HRV preparations of both major and minor serotypes. Most tonsils tested showed T cell proliferation, and responses to multiple serotypes in one tonsil were observed frequently. Responding T cells were CD4-positive and produced interleukin-2 and interferon-gamma but no interleukin-4. Thus, children respond to HRV, a proportion of the response is serotype-cross-reactive, and a Th1 reaction predominates. In addition to contributing to protection, this response may enhance expression of virus receptor and be implicated in the immunopathology of HRV infection.

Adolescent↗

Effects of killed and live attenuated influenza vaccine on symptoms and specific airway conductance in asthmatics and healthy subjects.

Killed and live influenza virus vaccines were given to asthmatics and healthy subjects to investigate symptoms and alterations in their respiratory performance after vaccination. Polyvalent killed influenza virus vaccine was given to 16 asthmatics and live attenuated influenza virus vaccine to 23 asthmatics and 21 healthy subjects. Fourteen of the 16 asthmatics vaccinated with the killed vaccine displayed a significant rise in serum antibody level as measured by a single radial haemolysis in gel (SRH test). 11 of the 23 asthmatics and 14 of the 21 healthy subjects vaccinated with the live attenuated vaccine displayed a significant rise in the SRH test. Among the subjects with no measurable initial antibodies and with a significant rise in the SRH test, one asthmatic vaccinated with the killed vaccine experienced symptoms of common cold with fever and dyspnoea 1 week after vaccination. Three asthmatics and four healthy subjects vaccinated with live attenuated vaccine experienced mild symptoms, mainly rhinorrhoea, cough and sore throat 2 to 3 days after vaccination. No alterations in specific airway conductance in asthmatics or in healthy subjects were observed. We conclude that both killed and live attenuated influenza virus vaccines are tolerated well by asthmatics and appear to be safe for asthma patients.

Adult↗

Simultaneous detection of herpes simplex virus types 1 and 2 by real-time PCR and Pyrosequencing.

BACKGROUND: Up to 80% of the US adult population has been exposed to herpes simplex virus (HSV) type 1, primarily during childhood. Also, approximately 20% of the US population has contracted genital herpes from HSV-2 infections. Clinical symptoms can present as fever, headache, malaise, myalgia, and cold sores/lesions that cause pain, itching, dysuria, and vaginal or urethral discharge. A recurrence of infection is common. HSV culturing is characterized by low sensitivity with variable success rates due to shipping conditions. OBJECTIVE: To design and validate a real-time PCR assay capable of simultaneously detecting each HSV subtype. STUDY DESIGN: ATCC-purchased HSV-1 and HSV-2 positive samples and HSV-1 and HSV-2 infected clinical specimens were assayed simultaneously with shared amplification primers and subtype-specific probes against the HSV glycoprotein B gene on a Rotor-Gene 3000 platform. Separately, two PCR reactions were performed in which one primer contained a 5' biotin modification. Single-stranded DNA from the amplicon was purified and Pyrosequenced. RESULTS: The quantitative range of the assay extended from 10(8) through 10(0) copies of each virus (r(2) > 0.991) and specificity was determined by non-amplification of 37 different human pathogens, including other herpesviruses such as VZV, CMV, and EBV. Sensitivity and specificity values of 100% were calculated by concordance analysis between the real-time PCR and the DNA Pyrosequencing results (HSV-1: n = 119, HSV-2: n = 120). Application of this assay to 4581 cervical swab specimens collected from women visiting physicians primarily in six states provided detection rates of 3.1% for HSV-1 and 7.6% for HSV-2. The average age of women infected with HSV-1 was 29.5 versus 35.6 for HSV-2. CONCLUSIONS: This procedure was demonstrated as both highly sensitive and specific for the detection of HSV-1 and HSV-2 in a single reaction. Also, the integration of Pyrosequencing analysis permitted an innovative and rapid verification for each subtype.

Adult↗

Etiology of AIDS: biological and biochemical characteristics of HTLV-III.

The newly identified human HTLV-III virus, the etiologic agent for AIDS, shares many of the biological and physicochemical properties common to a family of retroviruses named human T-cell leukemia (lymphotropic) viruses, or HTLV. Because of the similarities, and because of the uniform nomenclature for human T-cell leukemia (lymphotropic) viruses adopted at the first Cold Spring Harbor Meeting on HTLV (19, 79), this newly discovered virus associated with AIDS as HTLV-III was named HTLV-III. Other investigators making independent isolations of virus have suggested naming the virus lymphadenopathy virus or LAV (3, 16), immunodeficiency associated virus or IADV (48), AIDS-related virus (41). Immunological and nucleic acid comparison has now demonstrated that these viruses are, not surprisingly, very similar to HTLV-III (55, 63, 78). In view of the wide range of disease manifestations caused by the virus, and previous discussions concerning a uniform nomenclature for human T-lymphotropic retroviruses, it would seem ill-advised to restrict the name of this virus to one clinical manifestation of one disease. The frequent isolation of HTLV-III from patients with AIDS and ARC, the detection of antibodies specific for HTLV-III in nearly all patients with these diseases and in a high proportion of individuals at risk, and finally its effect on cells in vitro, leaves little doubt that HTLV-III is causatively involved in the development of these diseases. This etiologic association is further strengthened by the detection of HTLV-III infection in many instances where a direct cause-and-effect association can be made, e.g., hemophiliacs and children with AIDS, and blood from HTLV-III infected donors and the otherwise normal recipients of this blood who subsequently develop AIDS.

Acquired Immunodeficiency Syndrome↗

Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses.

Equine rhinoviruses (ERVs) are picornaviruses which cause a mild respiratory infection in horses. The illness resembles the common cold brought about by rhinoviruses in humans; however, the presence of a viraemia during ERV-1 infection, the occurrence of persistent infections and the physical properties are all more reminiscent of foot-and-mouth disease virus (FMDV). cDNA cloning and sequencing of the genomes of ERV-1 and ERV-2 between the poly(C) and poly(A) tracts showed that the serotypes are heterogeneous. Nevertheless, the genomic architecture of both serotypes is most similar to that of FMDV. Indeed, a comparison of the derived protein sequences of ERV-1 shows that their identity is greatest to FMDV. In contrast, most ERV-2 proteins are more related to encephalomyocarditis virus (EMCV) proteins than they are to FMDV or ERV-1. These results place ERV-1 alongside FMDV in the aphthovirus genus of the picornavirus family and indicate that this virus may serve as a model system for examining the biology of FMDV.

Amino Acid Sequence↗

Detection of human rhinoviruses and their molecular relationship using cDNA probes.

We describe here a cDNA:RNA hybridization system for the study of human rhinoviruses. We have constructed an M13 probe from the 5' end of the genome of rhinovirus 14 (HRV-14) and used this to detect directly viral RNA. Of the 56 human rhinoviruses so far investigated 54 or 96.4% gave clearly positive hybridization signals. However, the strength of this signal depended very much on the molecular relationship of these viruses. Thus, HRV-3, 4, 17, 72, and, to a slightly lesser extent, HRV-2, 6, 9, 13, 19, 31, 42, 49, 64, and 69 appear to be closely related to HRV-14 whereas HRV-5, 7, 8, 16, 32, 40, 45, 55, 56, 63, 80, 82, and 85 appear to be relatively divergent. Further, evidence is provided in this study that indicates that it would be feasible to use cDNA probes to detect human rhinoviruses in nasal washings. However, the sensitivity of detection was clearly affected by both the inclusion of inhibitors of endogenous RNase activity in the RNA extraction mixture and also in the method of extracting the viral RNA. From reconstruction experiments in nasal washings and under optimal conditions, we can detect virus at 10(2.8) TCID50/ml.

Common Cold↗

An evaluation of Echinacea angustifolia in experimental rhinovirus infections.

BACKGROUND: Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection. METHODS: Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis. RESULTS: There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer. CONCLUSIONS: The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Adult↗

Recurrent herpes labialis in a military brass band.

80-90% of the adult population is known to have neutralizing antibodies to herpes simplex virus type 1 (HSV1), of these 18-32% suffer from occasional recurrent herpes labialis (RHL). It is thought that local trigger factors as external traumata, UV-light and chemical stimuli, or systemic factors like fever or common cold, may induce RHL. The aim of the present study was to investigate the frequency of RHL in a military brass band and compare this with the frequency of the disease in a control population of soldiers from the same unit. Both populations were national servicemen aged 19-22 yr. The diagnosis of RHL was based on the presence of herpetic vesicles in the labial region. Of the diagnosed cases, 10% were confirmed by laboratory procedures according to standard methods. The incidence of RHL over a period of 8 months was twice as frequent in the group of brass and woodwind players as in the control group of soldiers from the same military unit. This may indicate that the mechanical trauma to the labial tissue which occurs during playing may cause the increased frequency of RHL in musicians.

Adult↗

Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity.

Excretion of herpes simplex virus (HSV) in the oral cavity was studied in eight human subjects with a history of herpes labialis. Serial intraoral specimens were obtained by gargling broth and examined for virus by centrifugal inoculation of primary human amnion cells. Forty-seven of 637 specimens (7.4%) contained HSV. The majority of isolates (62%) were found in clusters, and the rate of excretion was significantly increased during the common cold (21%) and after oral trauma (17%) (P = 0.001 and 0.04, respectively). Oral HSV excretion often occurred in parallel with episodes of herpes labialis but could not be attributed to viral contamination from a labial lesion. Each patient excreted only one strain of HSV type 1 as determined by restriction endonuclease analysis with KpnI and BamHI. Unexpectedly, prodromal symptoms of herpes labialis were commonly not followed by development of a lesion (false prodrome). False prodromes were associated with a high rate of oral HSV excretion (60%). Intraoral ulcers on the gingivae and hard palate were frequently associated with oral HSV excretion (31%) and are the most likely source of HSV in the oral cavity.

Adult↗

Light and scanning electron microscopy of nasal biopsy material from patients with naturally acquired common colds.

As our knowledge of the histopathology of common colds is very limited, we have undertaken a blind quantitative examination by scanning electron microscopy and light microscopy of 56 nasal biopsies, taken from 29 volunteers with naturally acquired colds. In agreement with earlier reports we found evidence of sloughing of epithelial cells, but in contrast to in vitro experiments, this did not result in a destruction of the epithelial lining, which by and large remained continuous, with structurally normal cell borders. There was a significant increase in the number of neutrophils, both in epithelium and in lamina propria, already on the 2nd day of the disease, and the hypothesis is advanced that the virus infection itself is the cause of the local neutrophilia. The only other abnormality demonstrated was an increased number of extracellular erythrocytes in the acute stage. The histological picture was not suggestive of an involvement of epithelial mast cells in the inflammation.

Adult↗