Latent adenovirus infection in COPD

Abstract

We have concentrated on the adenovirus as the source of the heightened inflammatory response of the lungs of patients with COPD. We have concentrated in particular on the responses to agents such as lipopolysaccharides and environmental particulates that contaminate the air we breathe, and we have accumulated evidence that the E1A gene of this virus could be the key player in this process. As other intracellular pathogens such as Chlamydia pneumoniae have recently been implicated in the pathogenesis of COPD, our studies on the adenovirus E1A could serve as the model for investigating the interaction between host and extrinsic factors in the chronic progression of this debilitating lung disease.

Figure 1

Transcription map of adenovirus early genes. There are six early transcription units (ie, E1A, E1B, E2A, E2B, E3, and E4), and each produces multiple transcripts. Arrows indicate the sequences transcribed and the direction of transcription. The gaps in the arrows indicate the position of introns. mu = map units.

Figure 2

Northern blot analysis comparing TLR2, TLR4, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) messenger RNA expression in control HBE cells (E1A−) and adenovirus E1A-expressing HBE cells (E1A+), which either were left untreated (−) or were stimulated with 10 μg/mL LPS for 6 h (LPS), and in unstimulated human peripheral blood monocytes. The complimentary DNA probes for the TLR2 and TLR4 messenger RNA were from Genentech Inc (South San Francisco, CA) and Tularik Inc (South San Francisco, CA), respectively.