Cytomegalovirus Is Implicated in COPD

It has always been obvious merely from looking at the scatter plots in old studies of lung function that, among both smokers and nonsmokers, certain individuals were distinctly abnormal. They had much higher rates of loss than the others. There was a higher proportion of abnormal individuals among the smokers, and, by ignoring these individual differences and lumping together all smokers versus all nonsmokers, the anti-smoking ideologues falsely implicated tobacco as the cause of chronic obstructive pulmonary disease (COPD).

T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease. C Lambers, S Hacker, M Posch, K Hoetzenecker, A Pollreisz, M Lichtenauer, W Klepetko, HJ Ankersmit. Clin Exp Immunol 2009 Mar;155(3):466-475. 64 patients and controls. "T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4(+)CD28(null) cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages." But this statement is a flagrant lie: "Our finding of increased CD4(+)CD28(null) T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients." In fact, infection by cytomegalovirus triggers the formation of CD4(+)CD28(-) T cells, and these cells are found exclusively in CMV-positive persons. Furthermore, for socioeconomic reasons, smokers are more likely to have been infected by CMV. CMV may also have been reactivated due to the use of immunosuppressive drugs. It is reasonable to allege that because of the health establishment's obsession with blaming smoking, COPD patients have been systematically denied the treatment they need.

Lambers - Clin Exp Immunol 2009 full article / PubMed Central
CMV Impairs Immunity - association of CD4(+)CD28(null) T cells with CMV has been known since at least 2002

The aging immune system and its relationship to the development of chronic obstructive pulmonary disease. G Sharma, NA Hanania,YM Shim. Proc Am Thorac Soc 2009 Dec 1;6(7):573-580. Review. They note that "Studies have also suggested that persistent herpes infection, cytomegalovirus (CMV) infection, or parasite antigens may significantly contribute to the increased levels of proinflammatory factors and contribute to a number of negative clinical consequences." Eight paragraphs later, they observe that "Even though most studies have demonstrated that aging resulted in loss of appropriate innate immune response, recent studies by Aoshiba and coworkers and by Lambers and colleagues report intriguing possible roles for CD4+, CD8+, and CD28null in COPD pathogenesis. They demonstrated that repetitive, chronic antigen exposure induces loss of CD28 expression with aging and that CD4+ CD28null and CD8+ CD28null cells of the adaptive immune system may contribute to COPD pathogenesis." Although directly relevant research had been published up to five years before, they never make the connection between the two. "Conflict of Interest Statement: G.S. received lecture fees from Pfizer and AstraZeneca (AZ) ($1,001–$5,000). N.A.H. served as a consultant for GlaxoSmithKline (GSK), Dey, and Novartis ($5,001–$10,000). He received lecture fees from GSK, AZ ($10,001–$50,000), and Genentech ($1,001–$5,000), and received grant support from GSK ($50,001–$100,000), Novartis ($10,001–$50,000), Boehringer Ingelheim ($50,001–$100,000), and Dey ($10,001–$50,000). Y.M.S. received grant support from Merck ($50,001–$100,000), the American Lung Association ($50,001–$100,000), the Jeffress Foundation ($10,001–$50,000), and FAMRI ($100,001 or more)."

Sharma / Proc Am Thorac Soc 2009 full article (pdf 8 pp)

This study is cited in the 2014 Surgeon General report, which misleadingly claims that "While oligoclonal expansion of CD4+ cells is documented in humans (Korn et al. 2005; Sullivan et al. 2005), the specificity of these T cells is not well-understood," when in fact it is known that those particular cells are absolutely specific for CMV. The study cited is: Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema. AK Sullivan, PL Simonian, MT Falta, JD Mitchell, GP Cosgrove, KK Brown, BL Kotzin, NF Voelkel, AP Fontenot. Am J Respir Crit Care Med 2005 Sep 1;172(5):590-596. "In addition, lung CD4+ T cells showed a significant increase in expression of the activation marker CD45RO. Finally, a significant number of lung CD4+ T cells had lost expression of the costimulatory molecule CD28. CD28 engagement is absolutely required for optimum activation of naive T cells. Conversely, memory T cells no longer require CD28-mediated costimulation for effector function. This expression pattern of both memory and activation markers confirmed that the T cells accumulating in and isolated from the lungs of patients with emphysema are phenotypically distinct from those circulating in blood and consist of activated effector memory T cells."

Sullivan - Am J Respir Crit Care Med 2005 full article / PubMed Central

Differences in the Distribution of CD4+ and CD8+ T Cells in Emphysematous Lungs. K Aoshiba, M Koinuma, N Yokohori, A Nagai, The Respiratory Failure Research Group in Japan. Respiration 2004;71:184-190. Lung tissue sections obtained from 10 smokers with pulmonary emphysema who had undergone lung volume reduction surgery. "The majority of CD4+ cells were located in the lung parenchyma of severe emphysematous lesions characterized by the lowest alveolar wall fraction (AA,aw). In contrast, more CD8+ cells were located in mild emphysematous lesions than in severe lesions." All patients had stopped smoking prior to surgery.

Aoshiba / Respiration 2004 full article

Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. AW Sylwester, BL Mitchell, JB Edgar, C Taormina, C Pelte, F Ruchti, PR Sleath, KH Grabstein, NA Hosken, F Kern, J. A Nelson, and LJ Picker. J Exp Med 2005;202(5):673-685. "We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average ∼10% of both the CD4+ and CD8+ memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8+ T cells and was rare." "[O]ur observation that ∼30% of adult subjects have HCMV-specific populations comprising >20% of their circulating CD4+ and/or CD8+ memory T cell repertoire suggests that HCMV-specific T cell responsiveness might be excessive in some individuals, perhaps with detrimental clinical effects." "...T cell recognition of HCMV is complex, often very broad, and poorly approximated by responses to any one or two HCMV ORFs."

Sylwester / J Exp Med 2005 full article

Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease. VV Polosukhin, JM Cates, WE Lawson, R Zaynagetdinov, AP Milstone, PP Massion, S Ocak, JW Lee, RP Bowler, AV Kononov, SH Randell, TS Blackwell. Am J Respir Crit Care Med 2011 Aug 1;184(3):317-327. Tissue specimens from 30 lifetime nonsmokers and 16 former smokers without COPD, 22 patients with mild-to-moderate COPD and 32 patients with severe-to-very-severe COPD; BAL fluid from 9 lifetime non-smokers, 8 former smokers without COPD, and 10 former smokers with COPD. "Areas of bronchial mucosa covered by normal pseudo-stratified ciliated epithelium were characterized by pIgR expression with SIgA present on the mucosal surface. In contrast, areas of bronchial epithelial remodeling had reduced pIgR expression, localized SIgA deficiency, and increased CD4(+) and CD8(+) lymphocyte infiltration. In small airways (< 2 mm), these changes were associated with presence of herpesvirus antigens, airway wall remodeling, and airflow limitation in patients with COPD." Funded by NIH and U.S. Department of Veterans Affairs.

Polosukhin - Am J Respir Crit Care Med 2011 full article / PubMed Central

Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease. G Hodge, V Mukaro, PN Reynolds, S Hodge. Clin Exp Immunol 2011 October; 166(1): 94–102. 34 controls, 15 smokers and 48 COPD subjects. "CD8/CD28null cells were increased in both current- and ex-smoker COPD groups; these cells expressed significantly more interferon (IFN)-γ, OX40, 4-1BB, CTLA4, granzyme and perforin when stimulated than CD8/CD28+ T cells. There were no changes in CD4/CD28null T cells." [CD8+CD28- cells also expand to control persistent CMV infection, but they mention cytomegalovirus nowhere, and speculate instead "that cigarette smoking may initiate a self-maintaining pathogenic process that inhibits resolution," and about "autoimmunity" rather than chronic infection. This is conspiracy of silence - cast]

Hodge - Clin Exp Immunol 2011 full article / PubMed Central

High levels of lung resident CD4+CD28null cells in COPD: implications of autoimmunity. K Hoetzenecker, A Mitterbauer, E Guenova, T Schweiger, P Altmann, M Zimmermann, H Hofbauer, L Beer, W Klepetko, HJ Ankersmit. Wien Klin Wochenschr 2013 Mar;125(5-6):150-155. "[W]e evaluated lungs from end-stage COPD patients and compared the levels of tissue infiltrating CD4+CD28null cells to systemic levels. We could show that CD4+CD28null cells are present in high amounts in lung tissue obtained from COPD GOLD IV patients suggesting a direct involvement of those cells in the pathophysiology of COPD. Furthermore, purified lung-resident CD4+ cells showed a stable proliferative response to lung specific elastin and collagen.These results further corroborate the role of autoreactive CD4+ cells in the maintenance of the inflammatory destruction in COPD."

Hoetzenecker - Wien Klin Wochenschr 2013 abstract / PubMed

COPD IS A SYSTEMIC, NOT LOCAL, DISEASE

Mitochondrial Abnormalities in COPD include tissues with no exposure to cigarette smoke

Systemic effects of COPD. M Decramer, F De Benedetto, A Del Ponte, S Marinari. Respir Med 2005 Dec;99 Suppl B:S3-10. "Chronic obstructive pulmonary disease (COPD) is characterised by a range of pathological changes of the respiratory system, including airflow limitation secondary to structural changes of the small airways and loss of alveolar attachments, inflammation, ciliary dysfunction, and increased mucous production. COPD also has significant systemic consequences... Although improving lung function and disease symptoms have been the main focus of COPD management, these parameters alone do not reflect the full burden of disease. More recent endeavours have highlighted the potential role of addressing physical limitations imposed by systemic alterations. It is evident that systemic manifestations are common in COPD. Indeed, many patients demonstrate a gradual and significant weight loss that exacerbates the course and prognosis of disease. This weight loss is often accompanied by peripheral muscle dysfunction and weakness, which markedly contribute to exercise limitation and impaired quality of life."

Decramer - Respir Med 2005 abstract / PubMed

Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD. HR Gosker, MK Hesselink, H Duimel, KA Ward, AM Schols. Eur Respir J 2007 Jul;30(1):73-79. "Mitochondrial number (0.34 versus 0.63 n.microm(-2)) and fractional area (1.95 versus 4.25%) were reduced in the vastus of COPD patients compared with controls."

Gosker / Eur Respir J 2007 full article

E1A oncogene enhancement of caspase-2-mediated mitochondrial injury sensitizes cells to macrophage nitric oxide-induced apoptosis. JR Radke, ZK Siddiqui, TA Miura, JM Routes, JL Cook. J Immunol 2008 Jun 15;180(12):8272-8279. "E1A expression did block cellular recovery from NO-induced mitochondrial injury and converted the reversible, NO-induced cytostasis response of cells to an apoptotic response. This viral oncogene-induced phenotypic conversion of the cellular injury response of mouse and human cells was mediated by an E1A-related increase in NO-induced activation of caspase-2, an apical initiator of intrinsic apoptosis. Blocking caspase-2 activation or expression eliminated the NO-induced apoptotic response of E1A-positive cells."

Radke - J Immunol 2008 abstract / PubMed

Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. L Puente-Maestu, J Pérez-Parra, R Godoy, N Moreno, A Tejedor, F González-Aragoneses, JL Bravo, FV Alvarez, S Camaño, A Agustí. Eur Respir J 2009 May;33(5):1045-1052. "Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease."

Puente-Maestu - Eur Respir J 2009 abstract / PubMed

Adenovirus Infection in COPD

Latent adenoviral infection in the pathogenesis of chronic airways obstruction. T Matsuse, S Hayashi, K Kuwano, H Keunecke, WA Jefferies, JC Hogg. Am Rev Respir Dis 1992 Jul;146(1):177-184. The American Review of Respiratory Disease and its successor, the American Review of Critical Care Medicine, is the organ of the American Thoracic Society, which was formed as a division of the American Lung Association.

Matsuse - Am Rev Respir Dis 1992 abstract / PubMed

Endotoxin-specific NF-kappa-B activation in pulmonary epithelial cells harboring adenovirus E1A. N Keicho, Y Higashimoto, GP Bondy, WM Elliot, JC Hogg, S Hayashi. Am J Physiol 1999;277(Lung Cell Mol Physiol 21):L523-L532. "Studies from our laboratory showed that greater copy numbers of the E1A DNA from Group C adenovirus are found in the lungs of smokers with chronic obstructive pulmonary disease than in smokers without airways obstruction and that E1A proteins are detected in lung epithelial cells of these patients."

Keicho / Am J Physiol 1999 full article

Effect of adenovirus E1A on ICAM-1 promoter activity in human alveolar and bronchial epithelial cells. Y Higashimoto, N Keicho, WM Elliot, JC Hogg, S Hayashi. Gene Expr 1999;8(5-6):287-297. "Because adenovirus E1A gene products are known to regulate the expression of many genes by interacting with cellular transcription factors, we postulated that E1A enhances the production of inflammatory mediators and exacerbates the inflammatory process in smokers' lungs." This is pure Political Correctness, because contrary to the lies we've been brainwashed with, most smokers don't have any such "inflammatory process" and some nonsmokers do.

Higashimoto - Gene Expr 1999 abstract / PubMed

New treatments proposed for chronic obstructive pulmonary disease. Lisa Melton, The Lancet Interactive 2000 Feb 5. "James Hogg (St. Paul's Hospital, Vancouver, Canada) believes that, in patients with COPD, latent adenoviral infection might amplify the inflammation that cigarettes trigger in all smokers. His team has detected large amounts of an adenoviral protein in lung samples from patients with COPD, localised to areas of inflammation and emphysema."

The Lancet Interactive 2000 Feb 5 / findarticles.com

Amplification of inflammation in emphysema and its association with latent adenoviral infection. I Retamales, WM Elliott, B Meshi, HO Coxson, PD Pare, FC Sciurba, RM Rogers, S Hayashi, JC Hogg. Am J Respir Crit Care Med 2001 Aug 1;164(3):469-473. These charlatans compare "patients with similar smoking histories and either no (n=7), mild (n=7), or severe emphysema (n=7), and illogically conclude that "cigarette smoke-induced lung inflammation [which most smokers don't have -cast] is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process."

Retamales - Am J Respir Crit Care Med 2001 abstract / PubMed
Retamales - Am J Respir Crit Care Med 2001 Full Article

(Comment on Retamales et al.) End-stage chronic obstructive pulmonary disease: the cigarette is burned out but inflammation rages on. SD Shapiro. Am J Respir Crit Care Med 2001 Aug 1;164(3):339-340.

Shapiro - Am J Respir Crit Care Med 2001 abstract / PubMed
Shapiro - Am J Respir Crit Care Med 2001 Full Article

[Latent adenovirus infection in chronic obstructive pulmonary disease.] B He, M Zhao, X Li. Zhonghua Jie He He Hu Xi Za Zhi 2001 Sep;24(9):520-523. "The E1A region of adenovirus was found in the epithelial cells of COPD and chronic bronchitis patients (27%), not found in the patients with asthma and normal volunteers. Furthermore, E1A DNA was much more commonly in the COPD patients (50%) than in the patients with chronic bronchitis (8%) (P<0.05). CONCLUSIONS: Latent adenoviral infection was present in the stable stage of COPD and may be related to the pathogenesis of the disease."

He - Zhonghua Jie He He Hu Xi Za Zhi 2001 abstract / PubMed

Role of latent viral infections in chronic obstructive pulmonary disease and asthma. JC Hogg. Am J Respir Crit Care Med 2001 Nov 15;164(10 Pt 2):S71-S75. A propaganda study with guinea pigs. Quoth Hogg: "Acute viral respiratory tract infections are well known to precipitate asthma attacks and acute exacerbations of chronic obstructive pulmonary disease, but their role in the pathogenesis of chronic disease is poorly designed." And why is this this case, Dr. Hogg? Haven't you and your ATS cronies known about the disintegrating effects of adenoviruses since the 1950s? And purposely stifled the research so you could blame smoking?

Hogg - Am J Respir Crit Care Med 2001 abstract / PubMed
Hogg - Am J Respir Crit Care Med 2001 Full Article

Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response. B Meshi, TZ Vitalis, D Ionescu, WM Elliot, C Liu, XD Wang, S Hyashi, JC Hogg. Am J Respir Cell Mol Biol 2002 Jan;26(1):52-57. Another rehash of Hogg's guinea pig study. Another question: Why does it seem as if James C. Hogg and his friends are the only ones allowed to investigate and/or publish on this subject, at least in the western literature?

Meshi - Am J Respir Cell Mol Biol 2002 abstract / PubMed
Meshi - Am J Respir Cell Mol Biol 2002 Full Article

COPD Prevalence in Lifetime Nonsmokers

While admitting that COPD occurs in only "15-20% of heavy, long-term cigarette smokers," they fail to acknowledge that 4 to 6% of lifelong nonsmokers have physician-diagnosed COPD as well (Chronic obstructive pulmonary disease in lifelong nonsmokers: results from NHANES. AS Whittemore, SA Perlin, Y DiCiccio. Am J Public Health 1995 May;85(5):702-706), with COPD defined as chronic bronchitis or emphysema. The lie the health establishment has been pounding into us for decades that COPD is "vanishingly rare" in lifelong nonsmokers is explicitly rejected by Whittemore et al. While spin-doctoring their work with the specious reservation that it failed to measure exposure to environmental tobacco smoke, they nevertheless admit that "Despite these reservations, some conclusions seem warranted. In particular, the disease is not vanishingly rare in nonsmokers. The overall prevalence in [never-smoking] adults aged 18 to 74 is about 4% to 6%."

Whittemore - Am J Public Health 1995 full article / PubMed Central

Mild and Moderate-to-Severe COPD in Nonsmokers. Distinct Demographic Profiles. C Behrendt. Chest 2005 Sep;128(3):1239. 13,995 examinees in the Third National Health and Nutrition Examination Survey, from 1988 to 1994. "Nonsmokers included never-smokers and former smokers with a < 5 pack-year smoking history who had never smoked cigars or pipes." "One fourth of mild and moderate-to-severe cases were nonsmokers. Among 7,526 nonsmokers, 4.7 ± 0.3% had mild COPD (n = 403; age, 60.9 ± 1.3 years) and were mostly female (82.5%), while 1.9 ± 0.3% had moderate-to-severe COPD (n = 92, age 39.3 ± 1.3) and were mostly male (88.1%)."

Behrendt - Chest 2005 full article

Airway obstruction in never smokers: results from the Third National Health and Nutrition Examination Survey. BR Celli, RJ Halbert, RJ Nordyke, B Schau. Am J Med 2005 Dec;118(12):1364-1372. "Never smokers represented 42% of the Third National Health and Nutrition Examination Survey population aged 30 to 80 years, with obstruction prevalence of 91 per 1000. Never smokers accounted for 4.56 million cases of obstruction, or 23% of the total burden."

Celli - Am J Med 2005 abstract / PubMed

COPD and Social Class

It has long been known that adenovirus infection is more common in the lower socioeconomic classes, just as Whittemore et al. found in their study of lifelong nonsmokers, where the percentages of physician-diagnosed COPD by income ranged from 2.7% to 5.6% in men, and 3.8% to 6.9% among women. Since smokers are more likely to be from the lower socioeconomic classes, smokers are more likely to be exposed to this infection. Exposure to infection, not ETS, is the most important confounder, and socioeconomic class is only an inadequate proxy for this true confounder. Furthermore, it has been known since 1962 that certain strains of adenovirus, notably Ad12, are known to be carcinogenic in animals, and the main difference between the carcinogenic and noncarcinogenic strains is in their ability to escape immune detection to cause a chronic infection. It has also long been known that adenoviruses interact with other oncogenic viruses, inlcuding polyoma, papilloma, and hepatitis viruses. The health establishment has purposely eschewed research of the appropriate level of sophistication in order to falsely blame smoking and passive smoking.

James C. Hogg

Adenoviruses were first discovered in 1953 (Isolation of a cytopathic agent from human adenoids undergoing spontaneous degeneration in tissue culture. WP Rowe, RJ Huebner*, LK Gilmore, RH Parrott. Proc Soc Exp Biol Med 1953;84:570-573; and: Recovery of new agents from patients with acute respiratory illness. MR Hilleman, JH Werner. Proc Soc Exp Biol Med 1954;85:183-188). (*This is our old "friend" Robert J Huebner of the National Cancer Institute's Cancer Virus Program, who failed to find any that caused cancer in humans despite the vast sums of money at his disposal.) For over 40 years, investigation of the role of adenoviruses in chronic diseases has been superficial or nonexistent. Only recently, particularly since the successful lynching of the tobacco companies, has a tiny trickle of this kind of research begun to appear, always with the politically correct anti-smoker spin, and under the supervision of big shots in the ALA's American Thoracic Society, particularly JC Hogg.

Meanwhile, the central investigator in many studies of adenoviruses and COPD, James C. Hogg, MD, of St. Paul's Hospital and professor of pathology at the University of British Columbia in Vancouver, has been the focus of defamatory propaganda. Dr. Terry Polevoy, who bills his website as the biggest anti-smoker site in Canada, attacks Hogg for accepting tobacco industry funding. But Polevoy fails to mention Hogg's long history of Politically Correct studies on both active and passive smoking, not to mention Hogg's listing in "Who's Who in ATS" of August 1997. Furthermore, Polevoy's supposed exposé of Hogg's long involvement with the tobacco companies, dating back to 1979 in Stanton Glantz's tobacco documents, actually implicates the tobacco lawyers in a long-term conspiracy with the anti-smokers. They could have been funding research on infection all along, but they didn't. In 1979, Hogg was "dosing guinea pigs with antigens to create inflammatory processes in the airways," in order to bolster the anti-smokers' claims.

Hogg / Polevoy website
"Who's Who in ATS" - James C. Hogg, MD / American Thoracic Society
1979 tobacco doc naming Hogg, BW-W2-03520 / tobacco document
James Cameron Hogg CV, 1990 / tobacco document

In 1983, Hogg was an International Advisor of the Aspen Lung Conference, sponsored by the Skull & Bones-controlled Webb-Waring Institute for Medical Research.

Polevoy also fails to mention the money that Hogg has gotten for this research from the US National Institutes of Health: "Emphysema research gets $1.26 million boost (November 2000). Pulmonary researcher Jim Hogg has received $1.26 million Cdn over four years from the US funding agency, National Institutes of Health, to pursue his groundbreaking research on the causes of emphysema..."

$1.26 million NIH grant, Providence Healthcare

Since Hogg is clearly a powerful member in good standing of the anti-smoker health establishment, Polevoy's attacks will have no effect on his professional status. Only ignorant members of the public (and media) would be influenced to believe that Hogg is a tobacco industry stooge so his work should be dismissed. And this enables the health establishment to maintain the two-faced system of science that it has nurtured over many decades: A public science of official lies and propaganda, versus a secret science that is known by only a tiny educated elite.

Adenovirus Mechanisms

Pulmonary Immunity to Viral Infection: Adenovirus Infection of Lung Dendritic Cells Renders T Cells Nonresponsive to Interleukin-2. AT Thiele, TL Sumpter, JA Walker, Q Xu, C-H Chang, RL Bacallao, R Kher, DS Wilkes. J Virol. 2006 Feb;80(4):1826-1836. "Results suggest that Ad-infected DCs induce T cells to be nonresponsive to IL-2 during primary coculture, as the addition of IL-2 in secondary cultures recovered T-cell proliferation. In vivo studies supported in vitro results showing that Ad infection resulted in lung T cells with decreased proliferative ability. This study demonstrates that Ad infection induces local immunoincompetence by altering DC-T-cell interactions."

Thiele / J Virol 2006 full article

Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cells. G Makedonas, N Hutnick, D Haney, AC Amick, J Gardner, G Cosma, AR Hersperger, D Dolfi, EJ Wherry, G Ferrari, MR Betts. PLoS Pathog 2010 Mar 5;6(3):e1000798. 23 normal donors. "While EBV and flu-specific CD8(+) T cells rarely upregulate perforin, CMV-specific cells often do and Ad stimulates an exceptionally strong perforin response. The differential propensity of CD8(+) T cells to produce either IL-2 or perforin is in part related to levels of CD28 and the transcription factor T-bet, as CD8(+) T cells that rapidly upregulate perforin harbor high levels of T-bet and those producing IL-2 express high amounts of CD28... Importantly, perforin and IL-2 are rarely co-expressed." A high proportion of IFN-γ producing adenovirus-specific CD8+ T cells also upregulated CD107a, a marker of degranulation, Fig. 3.

Makedonas - PLoS Pathog 2010 full article / PubMed CentralMakedonas / PLoS Pathog 2010 full article

Chronic infection

Latent species C adenoviruses in human tonsil tissues. CT Garnett, G Talekar, JA Mahr, W Huang, Y Zhang, DA Ornelles, LR Gooding. J Virol 2009 Mar;83(6):2417-2428. "All species C serotypes were represented in these tissues although Ad6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested) even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation."

Garnett / J Virol 2009 abstract

Other Viruses

Respiratory Viruses Augment the Adhesion of Bacterial Pathogens to Respiratory Epithelium in a Viral Species- and Cell Type-Dependent Manner. V Avadhanula, CA Rodriguez, JP DeVincenzo, Y Wang, RJ Webby, GC Ulett, EE Adderson. J Virol 2006 Feb;80(4):1629-1636. "All viruses enhanced bacterial adhesion to primary and immortalized cell lines. RSV and HPIV-3 infection increased the expression of several known receptors for pathogenic bacteria by primary bronchial epithelial cells and A549 cells but not by primary small airway epithelial cells. Influenza virus infection did not alter receptor expression. Paramyxoviruses augmented bacterial adherence to primary bronchial epithelial cells and immortalized cell lines by up-regulating eukaryotic cell receptors for these pathogens, whereas this mechanism was less significant in primary small airway epithelial cells and in influenza virus infections. Respiratory viruses promote bacterial adhesion to respiratory epithelial cells, a process that may increase bacterial colonization and contribute to disease. These studies highlight the distinct responses of different cell types to viral infection and the need to consider this variation when interpreting studies of the interactions between respiratory cells and viral pathogens."

Avadhanula / J Virol 2006 abstract

Miscellaneous

"Patients who are prescribed long term oxygen for chronic chest disease have usually been heavy smokers and many continue to smoke. Indeed research in the United States shows that half such patients are in rooms where someone is smoking within 10-15 feet of the machine--so the relative rarity of fire calamities (Respiratory Care 1983; 28: 906-12) reflects the fact that oxygen is neither explosive nor combustible. The plastic delivery tubing, however, will burn furiously if ignited while carrying pure oxygen." (News and Notes. British Medical Journal, 1983 Sep 17;287(6395):842.)

News and Notes. British Medical Journal, 1983 Sep 17 / tobacco document

See Also:

The Pig Lung Scam, Again and Again
CMV and Social Class

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cast 01-21-14