“Detection and significance of adenoviruses in cases of sudden infant death”.

Respiratory tract infections have been thought to act as a trigger mechanism in sudden infant death. In 118 autopsy cases of infant death, paraffin-embedded or frozen lung tissues were investigated by means of a nested polymerase chain reaction (PCR) to detect adenovirus (AV) DNA. The primers used are general primers and allow the detection of most pathogenic adenoviruses with high specificity and sensitivity and independently of devitalization of viruses or degradation of viral DNA. For the investigation three groups were established: there were 13 cases of unnatural death, 78 cases of natural death without histological signs of interstitial pneumonia, and 27 cases with interstitial pneumonia. The first group was AV negative. In the group without interstitial pneumonia AV was detected in 10.2% of the cases. In the group with interstitial pneumonia the frequency of AV detection was almost 26%. The results obtained demonstrate an association between interstitial pneumonia and detection of AV DNA, indicating that AV may play an important part in pulmonary infection in infants. Histological evidence of interstitial pneumonia was not observed in all AV-positive cases, perhaps because nonspecific virus-related changes occurred only in early stages of viral infection. Comparison of the AV frequency in SIDS (15%) and non-SIDS cases (4%) indicates an association between pulmonary AV infections and sudden death. These results support the working hypothesis of respiratory infections acting as a trigger mechanism in sudden infant death

Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children

BACKGROUND: Adenoviruses are the second most prevalent cause of acute lower respiratory infection of viral origin in children under four years of age in Buenos Aires, Argentina. The purpose of this study was to analyze the clinical features and outcome of acute lower respiratory infection associated with different adenovirus genotypes in children. METHODS: Twenty-four cases of acute lower respiratory infection and adenovirus diagnosis reported in a pediatric unit during a two-year period were retrospectively reviewed. Adenovirus was detected by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17 isolates was studied by restriction enzyme analysis with Bam HI and Sma I. RESULTS: Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%. Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7% (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 ±; 6 months, and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71% of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases; tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other respiratory viruses were negative. During hospitalization, fatality rate was 16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus, fatality rate for adenovirus type 7 reached 28.6% (4/14). CONCLUSIONS: These results show the predominance of adenovirus 7 and high lethality associated with the genomic variants 7h and 7i in children hospitalized with acute lower respiratory infection

Fiber Mediated Receptor Masking in Non-Infected Bystander Cells Restricts Adenovirus Cell Killing Effect but Promotes Adenovirus Host Co-Existence

The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI), and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses

The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution

Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad–erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models

“Detection and significance of adenoviruses in cases of sudden infant death”.

Respiratory tract infections have been thought to act as a trigger mechanism in sudden infant death. In 118 autopsy cases of infant death, paraffin-embedded or frozen lung tissues were investigated by means of a nested polymerase chain reaction (PCR) to detect adenovirus (AV) DNA. The primers used are general primers and allow the detection of most pathogenic adenoviruses with high specificity and sensitivity and independently of devitalization of viruses or degradation of viral DNA. For the investigation three groups were established: there were 13 cases of unnatural death, 78 cases of natural death without histological signs of interstitial pneumonia, and 27 cases with interstitial pneumonia. The first group was AV negative. In the group without interstitial pneumonia AV was detected in 10.2% of the cases. In the group with interstitial pneumonia the frequency of AV detection was almost 26%. The results obtained demonstrate an association between interstitial pneumonia and detection of AV DNA, indicating that AV may play an important part in pulmonary infection in infants. Histological evidence of interstitial pneumonia was not observed in all AV-positive cases, perhaps because nonspecific virus-related changes occurred only in early stages of viral infection. Comparison of the AV frequency in SIDS (15%) and non-SIDS cases (4%) indicates an association between pulmonary AV infections and sudden death. These results support the working hypothesis of respiratory infections acting as a trigger mechanism in sudden infant death

“Detection and significance of adenoviruses in cases of sudden infant death”.

Respiratory tract infections have been thought to act as a trigger mechanism in sudden infant death. In 118 autopsy cases of infant death, paraffin-embedded or frozen lung tissues were investigated by means of a nested polymerase chain reaction (PCR) to detect adenovirus (AV) DNA. The primers used are general primers and allow the detection of most pathogenic adenoviruses with high specificity and sensitivity and independently of devitalization of viruses or degradation of viral DNA. For the investigation three groups were established: there were 13 cases of unnatural death, 78 cases of natural death without histological signs of interstitial pneumonia, and 27 cases with interstitial pneumonia. The first group was AV negative. In the group without interstitial pneumonia AV was detected in 10.2% of the cases. In the group with interstitial pneumonia the frequency of AV detection was almost 26%. The results obtained demonstrate an association between interstitial pneumonia and detection of AV DNA, indicating that AV may play an important part in pulmonary infection in infants. Histological evidence of interstitial pneumonia was not observed in all AV-positive cases, perhaps because nonspecific virus-related changes occurred only in early stages of viral infection. Comparison of the AV frequency in SIDS (15%) and non-SIDS cases (4%) indicates an association between pulmonary AV infections and sudden death. These results support the working hypothesis of respiratory infections acting as a trigger mechanism in sudden infant death