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PubMed1978

[Experimental study of combined staphylococcal, streptococcal and adenovirus infections in tissue culture].

Associated adenoviral, staphylococcus, and streptococcus infection was studied in the cultures of cells HEp-2 and PAO. Under conditions of monoinfection the cell culture largely inhibited the reproduction of staphylococci, and failed to influence the streptococci. In double and triple associated infections staphylococci overcame the inhibitory action of the cell culture. The pathogenic properties of cocci (plasma coagulation, hemotoxic properties) grown in the cell culture both under conditions of monoinfection, and in associations, failed to change. In double and triple associated infections adenoviruses did reproduce, but in lower titre than in monoinfection. Under conditions of mixed infection cocci penetrated and reproduced in the cell cytoplasm more intensively than in monoinfection. The cytopathic action was determined by viral associate, and was identical by its character to adenoviral monoinfection. A statistically significant increase in the activity of aldolase and transaminase enzymes was noted in mixed infection. The changes in the enzyme activity proved to depend on the character of the associations studied.

Adenoviridae Infections↗

PubMed2005

Three nonfatal cases of neonatal adenovirus infection.

Neonatal adenovirus infection is considered a rare and fatal disease. Three nonfatal neonatal adenovirus infections manifesting as conjunctivitis or conjunctivitis with other nonspecific symptoms are described. Adenovirus DNA was detected by PCR in eye swabs from two patients and in both cerebrospinal fluid and eye swabs in the third patient.

Adenoviridae Infections↗

PubMed1989

Still's disease associated with adenovirus infection and defect in adenovirus directed natural killing.

Low natural killer (NK) activity towards adenovirus infected fibroblasts was detected in the peripheral blood of a child with Still's disease and was not normalised by the addition of interferon alfa or interleukin 2. NK cytotoxicity directed at K 562 target cells or polio infected fibroblasts was normal. This specific NK deficiency might have contributed to the development of the child's Still's disease.

Adenoviridae Infections↗

PubMed1998

Fatal adenovirus infections in infants probably infected with HIV.

Adenovirus infections occur commonly in infants and children but are rarely fatal. Although immunosuppression has been associated recently with fatal outcome of adenovirus infections, reports of major morbidity or mortality caused by adenovirus infection in HIV positive patients are infrequent. This is the first report on fatal adenovirus infections in presumably HIV-positive infants in Thailand. Three infants, aged 4, 8 and 5 months, were hospitalized with diagnoses of pneumonia and ARDS, pneumonia with hepatomegaly and ARDS, and pediatric AIDS with pneumonia, respectively. All the infants died within a few weeks after hospitalization. Serologic tests revealed positive anti-HIV in all three infants. Unfortunately, no additional investigation for definite diagnosis of HIV infection was employed. Pathological findings from autopsy and post mortem needle biopsies revealed adenovirus pneumonia in the first two infants, and massive adenovirus infection of the liver in the third infant. Diagnoses were based on characteristic light microscopic pathological findings, and demonstration of viral particles arranged in crystalline arrays in the nucleus of the infected cells by electron microscopy.

AIDS-Related Opportunistic Infections↗

PubMed2001

Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta.

The molecular mechanisms and pathologic significance of placental viral infections are poorly understood. We investigated factors that regulate placental infection by adenovirus, which is the most common viral pathogen identified in fetal samples from abnormal pregnancies (i.e., fetal growth restriction, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybridization, flow cytometry, and immunostaining revealed that placental expression of the coxsackievirus and adenovirus receptor (CAR) varied with gestational age and trophoblast phenotype. The CAR was continuously expressed in invasive or extravillous trophoblast cells but not in villous trophoblast cells. We postulate that the villous syncytiotrophoblast, which does not express CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravillous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune response to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cell types that expressed CAR. Consequently, we speculate that adenovirus infection of extra-villous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction.

Adenoviridae Infections↗

PubMed1980

[Dynamics of maternal and post-infection adenovirus antibodies in fowl].

The epizootological study of the adenovirus infections of poultry, conducted with the use of the serum virus-neutralizing test, gives a picture of the distribution of various serotypes of avian adenoviruses in the poultry population, or in the largest poultry stocks in Czechoslovakia. There is a description of the occurrence of type-specific antibodies in serums of different age categories of poultry acting against seven available virus serotypes. An ascending trend in positive findings of adenovirus antibodies was observed with increasing age of the birds. The dynamics of yolk or maternal antibodies was studied under experimental conditions after the application of virus antigen.

Adenoviridae↗

PubMed1981

Alterations to controls of cellular DNA synthesis by adenovirus infection.

Human adenovirus type 5 and temperature-sensitive mutants ts36, ts37, and ts125 induced cellular DNA synthesis in quiescent rodent cells at both permissive and nonpermissive temperatures. Cellular DNA synthesis induced by adenovirus type 5 or by serum required protein synthesis for both initiation and continuation, whereas viral DNA synthesis was not dependent upon continued protein synthesis once it was initiated. Both cellular and viral DNA replication was induced in adenovirus type 5-infected cells in the presence of dibutyryl cyclic AMP at concentrations which inhibited induction by serum which suggested that some of the controls of DNA synthesis in serum-treated and virus-infected cells are different. After adenovirus infection of quiescent cells, there was a decrease in the number of cells with G1 DNA content and an increase in cells with G2 diploid and greater DNA contents. Thus, adenovirus type 5 induces a complete round of cellular DNA replication, but in some cells, it induces a second round without completion of a normal mitosis. These results suggest that adenovirus type 5 is able to alter cell growth cycle controls in a way which may be related to its ability to transform cells.

Adenoviruses, Human↗

PubMed2003

Fatal disseminated adenovirus infections in immunocompromised patients.

Adenovirus has emerged as an important pathogen in immunocompromised patients, in whom disseminated disease occurs frequently and is associated with a high mortality rate. In a retrospective review of 1,847 consecutive autopsies, we identified 84 cases where adenovirus infection was suspected clinically. Adenovirus infection was confirmed at autopsy in 8 (10%) of 84 cases; all were immunocompromised patients. Six (75%) of these cases had disseminated adenovirus infection that contributed to death. Pathologic findings attributed to adenovirus infection included pneumonia with or without intra-alveolar hemorrhage, hepatic necrosis, enterocolitis with or without mucosal hemorrhage, epicardial hemorrhage, and ulcerations of the larynx, trachea, and ileum. This work shows that severe and fatal adenovirus infections are not infrequent, particularly in the immunocompromised population. Both clinicians and pathologists must become aware of the pathogenicity of adenovirus in this patient population, including its potential for causing life-threatening hemorrhage.

Adenoviridae↗

PubMed1995

Splicing of two weak 3' splice sites from the adenovirus major late region is enhanced in nuclear extracts from adenovirus infected cells.

The adenovirus major late transcription unit (MLTU) is an example of a complex alternatively spliced gene, in which more than 15 different 3' splice sites can be joined to a common 5' splice site. Maturation of the full repertoire of possible mRNAs requires late viral protein synthesis and occurs only at late stages of the infectious cycle (16-24 hpi). We are trying to decipher the mechanisms regulating alternative 3' splice site choice during the infectious cycle. Therefore, we examined the splicing activity of several 3' splice sites from the MLTU in vitro in nuclear extracts prepared from adenovirus infected cells (Ad NE) and from uninfected cells. The results suggest that pre-mRNAs with "weak" 3' splice sites (short, atypical polypyrimidine tracts) are activated and pre-mRNAs with long, prototypical polypyrimidine tracts are repressed in Ad NE. In fact, our data show a reciprocal correlation between the strength of a polypyrimidine tract, defined by its affinity for U2AF65K in vitro, and the efficiency of splicing in Ad NE. We are currently investigating the possible mechanisms responsible for this observed shift in 3' splice site choice during an adenovirus infection.

Adenoviridae Infections↗

PubMed1993

Clinical picture and epidemiology of adenovirus infections (a review).

Adenoviruses produce a variety of serious diseases in people of all ages. The mode of transmission of adenovirus infections includes respiratory, fomite, droplet, venereal, and faecal-oral routes. They have been shown to spread with ease in AIDS patients, in young children and in hospitalized patients. A constant rate of about 8% of world-wide reported virus infections were observed to be due to adenovirus infections. In the military, it can cause serious respiratory disease (ARD) of epidemic proportion in new recruits. The present commercial vaccine is prepared in unique triple-layered tablets containing live lyophilized virus. This vaccine has been taken by more than ten million subjects during the past 25 years with no adverse reaction and with near total eradication of ARD epidemics among new recruits at training centers. As the epidemiology of adenovirus diseases becomes more clearly defined, the need for and the possible role of potential vaccines, is becoming more evident.

Adenoviridae Infections↗

PubMed2005

Synthesis, cellular localization, and quantification of penton-dodecahedron in serotype 3 adenovirus-infected cells.

Adenovirus penton is a non-covalent complex composed of the penton base and fiber proteins, localized at the twelve vertices of the icosahedral virus capsid. In cells infected by adenovirus serotype 3 (Ad3), penton is found not only in the virus capsid but also self-assembled in dodecahedra formed through interactions between the twelve penton bases. In this study, the intracellular trafficking of penton proteins from the cytoplasm to the nucleus has been followed, and the nuclear re-arrangement induced by viral infection has been observed by electron microscopy of ultrathin sections. The amount of dodecahedra has been assessed in relation to the number of Ad3 infectious virions produced during the Ad3 replication cycle. It appears that dodecahedra are produced in a large excess over viral infectious particles and that they are located intranuclearly along the nuclear membrane of Ad3-infected cells at late times of infection.

Adenoviridae↗

PubMed1997

Adenovirus infections in immunocompromised patients.

Adenovirus infections have been reported in as many as one-fifth of bone marrow transplant (BMT) recipients and patients with acquired immunodeficiency syndrome (AIDS), and in a lesser, though still prominent, proportion of organ transplant recipients. The relative contributions of primary infections versus reactivations from latency in immunocompromised patients remain unclear. Compared with adult BMT recipients, pediatric BMT recipients appear to be infected by adenovirus more frequently and earlier in the post-transplant period. The diagnosis of adenovirus infection is complicated by the existence of > 40 viral serotypes, although certain subgroups are more likely to be involved in certain patient populations. Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, and gastroenteritis. The clinical and histopathologic features of adenovirus disease may resemble those of cytomegalovirus disease, potentially complicating the diagnosis. Risk factors for clinical adenovirus disease include the number of sites from which the virus is cultured and, in BMT recipients, the presence of moderate to severe acute graft-versus-host disease.

AIDS-Related Opportunistic Infections↗

PubMed1991

Mixed infection is common in children with respiratory adenovirus infection.

The presence of concomitant viral or bacterial infection was evaluated in 20 patients hospitalized for adenovirus infection of the middle or lower airways by using new serological methods for detection of both antigens and antibodies. Adenovirus infection was identified by measurement of antibodies with complement fixation test or by direct detection of viral antigen in nasopharyngeal aspirates. Mixed infection was present in 11 (55%) of the 20 patients. Viral coinfection was demonstrated in five (25%) and bacterial in nine (45%) patients. Bacterial coinfection was common, 67%, in children with an infection focus, pneumonia or acute otitis media, but rare, 13%, in those without it. Seroconversion to nontypable Haemophilus influenzae was indicated in six children; four of them were infants, four had pneumonia and three acute otitis media. Pneumococcal infection was indicated in two patients with pneumonia, both aged over two years. Chlamydia trachomatis was involved in one case. The results indicate that bacterial coinfection is common in respiratory adenovirus infection affecting lower airways, especially if pneumonia is present.

Acute Disease↗

PubMed2001

A syndrome of transient encephalopathy associated with adenovirus infection.

BACKGROUND AND OBJECTIVE: Adenovirus is a common pathogen in the pediatric population. Respiratory, gastrointestinal, or renal systems are often involved in adenovirus infections. Several neurologic syndromes have been attributed to adenovirus, such as adenovirus aseptic meningitis, myelitis, subacute focal encephalitis, and Reye-like syndrome. The purpose of this study was to describe the clinical features and encephalography findings in 7 infants treated in our center for a syndrome of transient encephalopathy associated with adenovirus infection. STUDY PARTICIPANTS: Three females and 4 males ages 7 to 34 months seen in our department between July 1983 and February 1984 and September 1998 and May 1999 presented with fever of at least 7 days' duration and a gradual decline in the state of alertness. Score on the Glasgow Coma Scale ranged from 9 to 12. Findings on lumbar puncture were normal. In all 7 patients, the encephalogram showed moderate to severe background slowing compatible with encephalopathy. All patients were catarrheal and had mild hepatomegaly with slight elevation of liver enzymes. Some had bronchopneumonia, diarrhea, and conjunctivitis either isolated or in combination. METHODS AND RESULTS: Adenovirus was isolated by immunfluorescence technique in all patients-from the sputum in 3 patients, nasopharynx in 5, conjunctiva in 4, and rectal swab in 5. In 5 patients, serotyping was performed by an antibody neutralization method. Adenovirus type 3 was ascertained from a nasal swab in 1 patient, sputum specimens in 3, throat swab in 3, and rectal cultures in 5. The clinical course was characterized by a progressive recovery of alertness. After several days, there was a complete reversal of neurologic findings. CONCLUSION: We suggest that this syndrome of transient encephalopathy is a distinct entity and should be considered as another of the several neurologic syndromes known to be associated with adenovirus infection.

Adenoviridae↗

PubMed2002

Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells.

Adenovirus infection of hematopoietic cells frequently requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of Coxsackie and adenovirus receptor (CAR) and alpha(v) integrin. The effect of treatment with FR901228 (depsipeptide), a histone deacetylase inhibitor in phase 2 clinical trials, was studied in K562 cells, granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells (PBMCs), and CD34+ peripheral blood stem cells (PBSCs). FR901228 increased CAR and alpha(v) integrin RNA levels and histone H3 acetylation. FR901228 treatment before adenovirus infection was associated with at least a 10-fold increase in transgene expression from a beta-galactosidase-expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were beta-galactosidase-positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, alpha(v) integrin, and acetylated histone H3 levels were observed in PBMCs from a patient treated with FR901228. These studies suggest that FR901228 can increase the efficiency of adenoviral infection in hematopoietic cells.

Adenoviridae↗

PubMed2001

Detection and confirmation of reptilian adenovirus infection by in situ hybridization.

Adenovirus infections are documented in at least 12 different species of reptiles. In contrast to their mammalian and avian counterparts reptilian adenoviruses are not well characterized as to their pathogenic potential and their ability to cause primary disease. In the diagnostic setting, fresh tissues are often not available for virus isolation, and the confirmation of reptilian adenovirus infections is dependent largely upon electron microscopy for the identification of intranuclear viral inclusions associated with histopathologic changes. The diagnosis of adenovirus infection in 2 different species of snake was confirmed by the application of DNA in situ hybridization. Using an aviadenovirus specific oligoprobe, adenoviral DNA was observed in the nuclei of hepatocytes, Kupffer cells, endothelial cells, and enterocytes. Electron microscopy of the liver confirmed the presence of intranuclear viral particles morphologically consistent with an adenovirus. DNA in situ hybridization on formalin-fixed tissues can serve as a suitable alternative to electron microscopy in the diagnosis of reptilian adenovirus infections. Both affected snakes had other concurrent diseases, suggesting that the adenovirus may not have been the primary pathogen.

Adenoviridae↗

PubMed1999

Adenovirus infection after pediatric bone marrow transplantation.

Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range -4 to +333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.

Adenoviridae Infections↗

PubMed1998

Stability of the contractile assembly and Ca2+-activated tension in adenovirus infected adult cardiac myocytes.

Adenovirus-mediated gene transfer into adult cardiac myocytes in primary culture is a potentially useful method to study the structure and function of the contractile apparatus. However, the consequences of adenovirus infection on the highly differentiated state of the cultured myocyte have not been determined. We report here a detailed analysis of myofilament structure and function over time in primary culture and after adenovirus infection. Adult rat ventricular myocytes in primary culture were infected with a recombinant adenovirus vector expressing either the LacZ or alkaline phosphatase reporter gene. Control and infected myocytes were collected at days 0-7 post-isolation/infection, and myofilament isoform expression was determined by SDS-PAGE and Western blot. Laser scanning densitometry showed that the alpha- to beta-myosin heavy chain ratio, the stoichiometry of the myosin light chains and the expression of the adult troponin T isoform did not change over time in culture or with adenovirus treatment. Importantly, examination of Ca2+-activated tension in single myocytes showed no change in the shape or position of the tension-pCa relationship in the control and adenovirus infected myocytes during primary culture. These results indicate that the structure and function of adult cardiac myocytes are stable in short term primary culture and are not affected by adenovirus infection per se, and therefore provide the foundation for the use of adenovirus-mediated myofilament gene transfer to study contractile apparatus structure and function in adult cardiac myocytes.

Adenoviruses, Human↗