Role of genetic susceptibility to latent adenoviral infection and decreased lung function.
BACKGROUND
Latent adenoviral infection may amplify cigarette smoke-induced lung inflammation and therefore play an important role in the development of chronic obstructive pulmonary disease (COPD). Adenoviruses can evade the human immune response via their 19-kDa protein (19K) which delays the expression of class I human leukocyte antigen (HLA) proteins. The 19K protein shows higher affinity to HLA-B7 and A2 compared with HLA-A1 and A3. The receptor for adenovirus (CXADR) and integrin beta(5) (ITGB5) are host factors which might affect adenovirus infection. Therefore, we investigated the contribution of HLA, CXADR, and ITGB5 genetic variants to the presence of the E1A gene and to level of lung function.


METHODS
Study subjects were assayed for HLA-B7, A1, A2 and A3 by PCR-based assays using allele-specific primers. Polymorphisms of the CXADR and ITGB5 genes were genotyped by PCR-based restriction fragment length polymorphism assays. Detection of adenoviral E1A gene was performed by a real-time PCR TaqMan assay.


RESULTS
E1A positive individuals had a lower FEV(1) compared with E1A negative individuals. However, there was no significant difference in E1A positivity rate between the high (HLA-B7 and A2) and low (HLA-A1 and A3) 19K affinity groups. There was also no significant difference in FEV(1) level between each affinity group. There was no significant difference in E1A positivity rate or lung function among the CXADR and ITGB5 genotypes.


CONCLUSIONS
Genetic variants in HLA, CXADR and ITGB5 do not influence latent adenoviral infections and are not associated with COPD.
Kasuga
Ikuma
I
The James Hogg iCAPTURE Centre, University of British Columbia, St Paul's Hospital, Vancouver, Canada.
Hogg
James C
JC
Paré
Peter D
PD
Hayashi
Shizu
S
Sedgwick
Edward G
EG
Ruan
Jian
J
Wallace
Alison M
AM
He
Jian-Qing
JQ
Zhang
Xiaozhu
X
Sandford
Andrew J
AJ
D000258:Adenovirus Infections, Human / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011991:Receptors, Virus / Q000235:genetics*; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006680:HLA Antigens; D039641:Integrin beta Chains; D011991:Receptors, Virus; C084344:integrin beta5