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PubMed1997

[Adenovirus CNS infections].

Adenovirus infections are very common diseases, especially upper respiratory infections and diarrhea in infants. Moreover, adenoviruses can occasionally produce CNS infections. The common causative adenovirus is type 7 for them, and they have been associated with pneumonia and epidemics of adenovirus in family outbreaks. Reye-like syndrome has rarely been reported. As AIDS and other immunocompromised patients have increased, new reports of adenovirus CNS infections have also increased. Of course the immunosuppressed conditions have included lymphoma, transplant etc. In the near future, long term care for immunocompromised patients will have a crisis of adenovirus CNS infection. On the other hand, adenovirus CNS infections are difficult to diagnose precisely without special facilities, due to the need for adenovirus cultivation from CSF. In addition, the diagnosis may have limitations due to the many subtypes of adenovirus. Despite the benefits of PCR methods, standard laboratory testing procedures are still not established for diagnosis.

Adenoviridae Infections↗
PubMed1998

Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance.

Adenovirus infection occurs in 10% of pediatric orthotopic liver transplant recipients; however, no cases have been described in adult liver transplant recipients. A retrospective review of 191 adults who underwent liver transplantation from January 1988 through October 1995 was done to describe the incidence and clinical significance of adenovirus infection in this population. There were 11 (5.8%) patients with 16 cultures positive for adenovirus. Sites of isolation were urine (9), blood (2), liver biopsy (2), colonic biopsy (1), lung biopsy (1), and stool (1). Adenovirus infection was classified as either disease or asymptomatic infection. There were 7 cases of adenovirus disease (2 definite, 1 probable, and 4 possible). Disease was disseminated in 3 patients: All had pneumonia and 2 died. Of the 3 patients with pneumonia, 2 had evidence of multiorgan involvement. Adenovirus disease occurs in adult orthotopic liver transplant recipients and may be associated with significant morbidity and occasional mortality.

Adenoviridae↗
PubMed1992

Participation of immune complexes in adenovirus infection.

To determine the participation of immune complexes during adenovirus infection, we evaluated serum and necropsy specimens of patients with confirmed adenovirus infection of the lower respiratory tract. In lung and kidney from seven dead patients, immunofluorescence revealed the presence of hexon, immunoglobulins and complement. These patients had clinical manifestations of kidney dysfunction. In dead patients (3/3 in whom serum was available) neither anti-adenovirus antibodies nor adenovirus-specific immune complexes could be found in the final stage of the infection. However, two of these patients had anti-adenovirus antibodies and immune complexes in samples obtained early in the infection. Most patients (16/19) who survived the infection had circulating anti-adenovirus antibodies. Half also had immune complexes specific for adenovirus in some moment of the illness. This suggests that immune complexes arise during respiratory infection by adenovirus, probably contributing to its clinical picture.

Adenovirus Infections, Human↗
PubMed2003

Adenovirus DNA in serum of children hospitalized due to an acute respiratory adenovirus infection.

Serum samples from 68 immunocompetent infants (mean age, 12.6 months) with an acute adenovirus infection of the respiratory tract (39 experiencing their first adenovirus infection) were tested for the presence of adenovirus DNA, to investigate whether viral dissemination via the blood is usually present in the immunocompetent patient. Using a nested polymerase chain reaction assay, adenovirus DNA could be detected in acute-phase serum samples from 28 (41%) children. Adenovirus DNA was never found in follow-up serum samples, indicating a short period ( approximately 1 week) of viral dissemination. In children experiencing their first adenovirus infection, viral DNA could be detected in 72% of the acute-phase serum samples collected within the first week after onset of symptoms. Adenovirus DNA could also be detected in 25% of the acute-phase serum samples from patients with reinfection.

Acute Disease↗
PubMed1992

Segregation of viral double-stranded and single-stranded DNA molecules in nuclei of adenovirus infected cells as revealed by electron microscope in situ hybridization.

Formation of progeny viruses in the nuclei of HeLa cells infected with adenovirus type 5 was studied at the ultrastructural level by in situ hybridization techniques allowing specific detection of either viral double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA). Prior to the initiation of replication of viral genomes, infective DNA molecules which entered the nucleus of the target cell were randomly distributed among host chromatin fibers including nucleolus-associated chromatin. They were double-stranded, that is, without single-strand breaks. Such association of viral DNA with host condensed chromatin also occurred in mitosis. The initiation of viral genome replication occurred simultaneously with the appearance in the nucleoplasm of small fibrillar regions containing intermingled viral dsDNA and ssDNA. Later, at the intermediate stage of nuclear transformation, viral dsDNA and ssDNA molecules were almost entirely separated into two contiguous substructures. At this stage, viruses were observed occasionally in the vicinity of viral ssDNA accumulation sites. Still later, an additional substructure developed in the centre of the nucleus which consisted of large quantities of viral dsDNA, traces of viral ssDNA and abundant viruses. Portions of viral ssDNA were attached to some viruses even at late stage of nuclear transformation, an association which strongly suggests the occurrence of encapsidation of at least some of the viral genomes while they are still engaged in replication.

Adenovirus Infections, Human↗
PubMedDate not supplied

Adenovirus infection of the cervix.

A case is recorded in which intranuclear inclusions suggesting adenovirus infection were recognized in a routine Papanicolaou smear. The patient was recalled for virologic studies and adenovirus type 19 was cultured from the cervix. The patient had a recent history of systemic illness with conjunctivitis, and a friend had conjunctivitis at the same time which was also proven to be due to adenovirus of the same serotype. This is the first reported instance in which adenovirus infection of the cervix suspected on cytologic findings has been confirmed by virus culture.

Adenoviridae Infections↗
PubMed1970

Adenovirus infections in Manitoba.

This review of adenovirus infections in Manitoba over a five-year period is introduced with a brief presentation on the structure-function relationships of the adenoviruses. Extensive research has resulted in the accumulation of a great deal of basic information, far surpassing our knowledge about the infections that these viruses produce in man. More research is needed on the epidemiological and clinical aspects of these diseases, including methods for prevention and treatment, and earlier methods of diagnosis.Features of 216 adenovirus respiratory infections diagnosed from 1963 to 1967 are reviewed and presented. All infections were diagnosed by showing a four-fold or greater increase. In addition, an adenovirus was isolated from many of the infections. These infections occurred every year in substantial numbers and they were seen during each month of the year, although they were more frequent and severe in the winter. Infants and younger persons were often affected. The most severe disease was a pneumonitis which occurred mainly in infants. Associated symptoms usually arose from the gastrointestinal tract, and were sufficiently common to indicate that one should suspect an adenovirus infection when respiratory and gastrointestinal symptoms occur together in a child.The possible role of adenoviruses in the etiology of other than respiratory diseases is discussed and the features of 96 possible non-respiratory infections are presented. Further work will be required to establish a definite etiologic role of the adenoviruses in most of these infections.

Adenoviridae Infections↗
PubMed2006

Assessment of adenovirus infection in adult lung transplant recipients using molecular surveillance.

BACKGROUND: Little is known about adenovirus infections in adult lung transplant recipients. Because the virus can establish latency, re-activation may be relatively common after transplantation. METHODS: We assessed adenovirus infection in 80 adult lung transplant recipients. Adenovirus polymerase chain reaction (real-time PCR assay; limit of detection approximately 25 copies/ml plasma) was done on plasma samples collected at regular intervals until 1 year post-transplant. RESULTS: Adenovirus DNA was detected in 18 of 80 patients (22.5%) and in 19 of 595 (3.4%) plasma samples up to 12 months post-transplant. Median time to detection of viremia was 134 days post-transplant (range 1 to 370 days). Median viral load was 180 copies/ml plasma (range 50 to 360 copies/ml). Symptoms were evaluated at the time of adenovirus detection: 14 of 18 (78%) patients were asymptomatic; 4 of 18 (22%) patients had otherwise unexplained febrile/flu-like illness that resolved spontaneously. Adenovirus was not found to be a trigger for acute rejection. No detrimental effect on pulmonary function was seen immediately after adenovirus infection. CONCLUSIONS: Adenovirus viremia is common in adult lung transplant recipients. In contrast to findings on adenoviral pneumonitis in lung transplant recipients, isolated episodes of low-level viremia are self-limited and do not trigger acute rejection or a decline in pulmonary function.

Adenoviridae↗
PubMed1995

p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins.

Adenovirus E1B 19K protein prevents premature death of adenovirus-infected cells. Viral mutants (19K mutants) defective in the 19K protein induce enhanced cell death, resulting in fragmentation of viral and cellular DNA. The 19K protein can also suppress the effects of certain external cell death-inducing stimuli, such as tumor necrosis factor alpha and various DNA-damaging agents that induce apoptosis. We have examined viral infection of permissive human cells and nonpermissive rat cells to determine if the 19K mutant induces apoptotic or necrotic type of cell death. Infection of normal rat kidney cells with an adenovirus type 2 19K deletion mutant induces internucleosomal DNA fragmentation and condensation of nuclear chromatin. Electron microscopic examination of these cells revealed the presence of condensed subnuclear bodies characteristic of apoptosis. In contrast, infection of human A549 cells induces random DNA fragmentation, and these cells do not exhibit characteristic condensation of the nuclear chromatin but contain enlarged nuclei loaded with virus particles. Therefore, it appears that adenovirus infection induces both apoptotic and necrotic types of cell death, depending on the cell type. Both types of cell death can be suppressed by E1B 19K protein. Similarly, a recombinant adenovirus expressing the human Bcl-2 protein but lacking the E1B proteins can efficiently suppress both apoptotic and necrotic cell death induced by adenovirus infection. The requirement of p53 tumor suppressor protein in adenovirus-induced cell death was investigated by infection of human Saos2 and mouse p53 nullizygous (p53-/-) cells lacking p53 tumor suppressor protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviridae Infections↗
PubMed2002

Serum C-reactive protein in children with adenovirus infection.

OBJECTIVES: (1) To evaluate serum C-reactive protein (CRP) concentrations in children with adenovirus infection, and (2) to compare CRP concentrations in adenovirus and influenza virus infection. PATIENTS AND METHODS: Retrospective, comparative single-center study conducted in Emergency Department patients of a paediatric tertiary care center. Comparison of CRP in adenovirus infection and influenza was performed in patient groups stratified according to age and duration of fever. RESULTS: In 87 children with adenovirus infection (median age, 1.5 years; interquartile range, 0.9-3.0), CRP levels of <2 mg/L, <10 mg/L, and <100 mg/L were found in 4 (4%), 12 (13%), and 66 (76%) patients, respectively. Median CRP in the children with adenovirus infection and in 130 children with influenza was 49 mg/L (21-96) and 9 mg/L (3-20), respectively (p = 0.001). A statistically significant difference remained when these 2 patient groups were stratified according to age (</=2 vs. >2 years) and duration of fever (</=3 vs. >3 days) (p <0.001). In adenovirus infection CRP concentrations were unrelated to age, duration of fever and severity of illness, as judged by the extent of mucosal involvement and by the frequency and duration of hospitalisation. CONCLUSION: Paediatric adenovirus infection is associated with substantially elevated CRP concentrations in the absence of secondary bacterial infection. CRP levels were independent of the duration of illness, indicating that adenoviruses trigger an immediate inflammatory host response resembling invasive bacterial infection.

Adenoviridae Infections↗
PubMed1993

Antiviral agents for ocular adenovirus infections.

Despite significant knowledge of the molecular biology and genetics of adenovirus, no specific antiviral agent has been developed for use in adenovirus infections. This contrasts with the situation in herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections, in which antiviral agents target specific enzymes. Antiviral agents active against HSV and interferons have been used in the treatment of ocular adenovirus infections with limited effect. Some newer nucleoside analogues have inhibitory activity against adenovirus in vitro and their effect is being assessed in newly developed animal models. Live vaccines have been used in both the United States and Canada to protect military recruits against adenovirus-induced respiratory disease. However, the inoculating strains are not normally associated with epidemic keratoconjunctivitis (EKC). There is a low prevalence of antibody against strains of adenovirus inducing EKC. Until such time as specific antiviral agents against adenovirus are developed, the mainstays of therapy will remain topical antibiotics to eliminate any secondary bacterial infection and topical steroids to suppress the immune response against adenovirus or adenovirus-infected cells. Neither form of treatment is adenovirus specific.

Adenovirus Infections, Human↗
PubMed1997

Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection.

Although recombinant adenoviruses are attractive vectors for gene transfer to airway epithelia, they have proven to be relatively inefficient. To investigate the mechanisms of adenovirus-mediated gene transfer to airway epithelia, we examined the role of adenovirus fiber and penton base, the two proteins involved in attachment to and entry of virus into the cell. We used human airway epithelia grown under conditions that allow differentiation and development of a ciliated apical surface that closely resembles the in vivo condition. We found that addition of fiber protein inhibited virus binding and vector-mediated gene transfer to immature airway epithelia, as well as to primary cultures of rat hepatocytes and HeLa cells. However, fiber protein had no effect on vector binding and gene transfer to ciliated airway epithelia. We obtained similar results with addition of penton base protein: the protein inhibited gene transfer to immature epithelia, whereas there was no effect with ciliated epithelia. Moreover, infection was not attenuated with an adenovirus containing a mutation in penton base that prevents the interaction with cell surface integrins. These data suggest that the receptors required for efficient infection by adenovirus are either not present or not available on the apical surface of ciliated human airway epithelia. The results explain the reason for inefficient gene transfer and suggest approaches for improvement.

Adenoviridae↗
PubMed2004

Adenovirus infections in stem cell transplant recipients: recent developments in understanding of pathogenesis, diagnosis and management.

Adenovirus is increasingly recognized as an important pathogen in stem cell transplant recipients, reflecting increased awareness about the virus, together with changes in transplant practice such as the performance of more high-risk transplants, and improvements in diagnostic methods. In retrospective studies, the reported incidence of adenovirus infections ranged between 4-20% with a similar variation in the proportion of patients developing invasive disease. In contrast, the incidence of adenovirus infection varies between 20-30% in recent prospective studies on T-cell depleted or mismatched allografts and about 30-40% of these patients develop invasive disease. These prospective studies have established a relationship between the risk of invasive adenovirus disease and a number of factors such as the extent of T-cell depletion, the intensity of immunosuppressive therapy and the kinetics of lymphocyte recovery post-transplant. Polymerase chain reaction (PCR) assays to detect adenovirus DNA in peripheral blood have shown a strong correlation between viremia and the risk of disseminated adenovirus disease. These developments have led to the possibility of a preemptive antiviral treatment strategy for asymptomatic adenovirus infections. In addition, a better understanding of the interactions between adenovirus and host immune system in the post-transplant setting might enable development of effective immunotherapeutic strategies against adenovirus infections.

Adenoviridae Infections↗
PubMed1992

Virus-associated RNAs (VA-I and VA-II). An efficient target for the detection of adenovirus infections by in situ hybridization.

The identification of adenovirus in tissue can be difficult. In situ hybridization for adenovirus nucleic acids may aid in the demonstration of adenovirus infections. To develop a probe against adenovirus, a 978 bp fragment of DNA containing the VA-I, VA-II, and a portion of the L-1 regions of the adenovirus type 2 genome was cloned into the SK+ vector. These regions were selected because they are generally conserved among adenoviruses and are abundantly transcribed during the lytic cycle. Sense and antisense tritium or Digoxigenin-labeled riboprobes were generated using in vitro transcription and applied to formalin-fixed paraffin-embedded sections of HeLa cells infected with adenovirus type 2. Extensive in situ hybridization of the antisense riboprobe to HeLa cells with cytopathic changes was found. The number of cells to which the probe hybridized decreased proportionately with dilution of infected with noninfected cells. The control sense riboprobe showed only scattered breakthrough hybridization and in these cells hybridization was mainly located in the nucleus. Northern blot analysis of RNA from infected HeLa cells confirmed the in situ hybridization results. No hybridization was detected when cultured cells infected with herpes simplex virus, Epstein-Barr virus, cytomegalovirus, or human immunodeficiency virus were examined. Specific hybridization was detected in tissues obtained at autopsy from four patients with culture proven adenovirus infection. These observations suggest that this probe is useful in the diagnosis of adenovirus in formalin-fixed paraffin-embedded material.

Adenoviridae Infections↗
PubMed2001

Rapid and sensitive diagnosis of human adenovirus infections by a generic polymerase chain reaction.

A new adenovirus specific nested polymerase chain reaction (PCR) method is described. It was designed inside the hexon protein gene of the adenovirus genome, and was able to detect DNA of all 47 human adenovirus types in a wide range of clinical samples. A sensitive internal control system able to assure proper analytical conditions for the amplification of as few as 100 molecules of a heterologous DNA was included to avoid false negative results. Sensitivity was estimated at about 10 molecules per tube of a plasmid containing an insert of the first amplification product. The method was able to detect adenovirus infection in 31/43 conjunctival scrapings from patients with acute kerato conjunctivitis 10/40 nasopharyngeal aspirates from patients admitted to hospital with acute respiratory disease and 2/26 urine samples from patients with haemorrhagic cystitis with better sensitivity than cell culture or rapid diagnosis by antigen detection by immunofluorescence (IF) in the case of respiratory specimens. Only two of 17 stools positive for a group F adenovirus specific latex immunoassay were PCR negative. The internal control system avoided a false negative result on another two stool samples. In conclusion, the method described below was shown to be useful for rapid diagnosis of adenovirus infections with higher sensitivity than antigen detection by IF.

Adenovirus Infections, Human↗
PubMed1991

Neonatal adenovirus infection: four patients and review of the literature.

Four newborns with adenovirus infection are described, and the profile of neonatal adenovirus disease is outlined based on the cases of these newborns and nine previously described. Characteristic historical features included prolonged rupture of membranes, maternal illness, vaginal delivery, and onset of illness within the first 10 days of life. Clinical findings included lethargy, fever or hypothermia, anorexia, apnea, hepatomegaly, bleeding, and progressive pneumonia. Thrombocytopenia, coagulopathy, and hepatitis were typical laboratory manifestations. Illness was severe and generally unremitting; only two survivors have been reported. Pathologic changes were prominent in lung, liver, and brain. Virus isolates, predominantly serotypes 3, 7, 21, and 30 were obtained from multiple sites and organs. Epidemiologic evidence suggests that viral acquisition from the mother, perhaps via the birth canal, is a major mode of transmission. Neonatal adenovirus infection, which is frequently disseminated and generally fatal, should be considered in the differential diagnosis of neonatal sepsis and pneumonia.

Adenovirus Infections, Human↗
PubMed1996

Comparison of primer sets for detection of fecal and ocular adenovirus infection using the polymerase chain reaction.

Adenoviruses of subgenus F (types 40 and 41) cause infantile gastroenteritis and adenoviruses principally of types 1-7 are found in feces during respiratory or generalized infections. Adenoviruses (mostly types 3, 4, 8, 19, or 37) are also linked with follicular or epidemic conjunctivitis. The diagnostic efficiency of the polymerase chain reaction (PCR) for adenoviruses was assessed using genus-reactive primers H1 and H2 or JCH1 and JCH2 or subgenus F-specific primers F1a and F2a. With diarrheal stool specimens containing subgenus F adenoviruses, F1a/F2a PCR achieved at least as high a positivity rate (75/76 [99%]) as electron microscopy (72/76 [95%]) and was more sensitive than polyclonal antibody-based immune electron microscopy (IEM) for subgenus identification (75/76 [99%] vs. 66/76 [87%], P = 0.008). Twenty-three subgenus F strains untypeable by monoclonal antibody-based IEM were typed as 40 (n = 4) or 41 (n = 19) by Hha I digestion of the PCR product. The genus-reactive primer pairs provided DNA amplification assays of generally equal efficiency on conjunctival swab specimens though possible nucleic acid degradation in DNA extracts during storage could have meant that JCH1/JCH2 PCR was truly the more sensitive. The use of either genus-reactive primer set on fecal specimens cannot be recommended because, although the positivity rates with subgenus F PCR positive specimens were high (70/75 [93%] for H1 and H2, 14/15 [93%] for JCH1 and JCH2), the detection rates were disappointing with similar specimens yielding nonsubgenus F adenoviruses.

Adenoviridae Infections↗
PubMed1993

Promotion of cell adhesion on fibronectin during adenovirus infection of KB cells.

Cytopathic effects of adenovirus-infected human cells consist of rounding and detachment from the substrate at late times postinfection. It is not known, however, whether any changes in cell adhesion are induced by adenoviruses before cytopathic effects become evident. We show here that attachment and spreading of human adenovirus type 2 (Ad2)-infected KB cells on fibronectin (FN) are, unexpectedly, promoted at intermediate times postinfection. The promotion of spreading by Ad2 is not only on fibronectin but also on laminin and vitronectin. In contrast, Ad2 or Ad5 mutants defective in the E1b 19-kDa function did not lead to a promotion in cell attachment but they led to a promotion in cell spreading. Inhibition of spreading of Ad2-infected KB cells on FN by the peptide Gly-Arg-Gly-Asp-Ser-Pro is partial, although it is complete in uninfected KB cells. We found, however, that Ad2 infection does not significantly change the levels of expression of beta 1 integrin mRNA and FN receptor polypeptides. Our results thus suggest that adenovirus infection leads to a promotion in adhesion through influencing integrin molecules without altering the quantity and/or through activation in the cytoskeleton or some other pathway.

Adenoviridae Infections↗