Survey of KI, WU, MW, and STL Polyomavirus in Cancerous and Non-Cancerous Lung Tissues.

BACKGROUND/AIMS: The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues. The aim of the present study was to examine the DNA prevalence of these polyomaviruses in cancerous and non-cancerous lung tissue samples, in order to study the possible site for viral replication and/or persistence, and the potential association of these viruses with lung carcinogenesis as well. METHODS: 100 cancerous and 47 non-cancerous, formalin-fixed paraffin-embedded lung tissue samples were studied for KIPyV, WUPyV, MWPyV, and STLPyV by real-time PCR. RESULTS AND CONCLUSION: Neither of the viruses was found in samples from small-cell, non-small-cell (adenocarcinoma, squamous-cell carcinoma and large-cell neuroendocrine lung cancer), mixed-type and non-differentiated lung carcinoma, and non-cancerous lung tissues (from patients with pneumonia, emphysema and fibrosis).

HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype.

While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Our data indicate that HIV binds to but does not replicate in BCs. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by upregulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced "destructive" phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD.

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.

Cytomegalovirus enteritis manifesting as recurrent bowel obstruction and jejunal perforation in patient with acquired immunodeficiency syndrome: rare report of survival and review of the literature.

BACKGROUND: Cytomegalovirus (CMV) enteritis presenting with perforation in the setting of acquired immunodeficiency syndrome (AIDS) represents a particularly deadly combination. METHODS: Case report and review of the pertinent literature. CASE REPORT: The authors report a patient with AIDS and CMV enteritis presenting as recurrent small-bowel obstruction and leading to perforation of the jejunum with subsequent survival. CONCLUSION: This is believed to represent the second case in the English-language literature of survival after CMV-induced small intestinal perforation in a patient with AIDS.

Persistent pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of AIDS.

Human immunodeficiency virus (HIV)-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with subclinical infection has been postulated to promote COPD. Persistence of Pneumocystis is associated with HIV infection and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus model of HIV infection to study pulmonary effects of Pneumocystis colonization. Simian/human immunodeficiency virus-infected/Pneumocystis-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Increased levels of T helper type 2 cytokines and proinflammatory mediators in bronchoalveolar lavage fluid coincided with Pneumocystis colonization and a decline in pulmonary function. These results support the concept that an infectious agent contributes to the development of HIV-associated lung disease and suggest that Pneumocystis colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression, thus identifying potential therapeutic targets for COPD.

Correlation of HIV-1 detection and histology in AIDS-associated emphysema.

HIV-seropositive individuals are at an increased risk for an accelerated form of emphysema. The purpose of this study was to determine the distribution of HIV-1 RNA in lung tissues and correlate this with the histologic findings and expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas of histologically normal lung, very rare HIV-1-infected cells were evident. In contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag RNA was evident primarily in macrophages; infected pneumocytes were also seen. Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of emphysema. Colabeling experiments documented that MMP expression was found primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected macrophages. These results suggest that AIDS-related emphysema may be due, in part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and concomitant up-regulation of MMP expression in the neighboring, noninfected cells.

Amplification of inflammation in emphysema and its association with latent adenoviral infection.

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Effectiveness of influenza vaccine in reducing hospital admissions during the 1989-90 epidemic.

The effectiveness of influenza vaccine in reducing hospital admissions for pneumonia, influenza, bronchitis, or emphysema was assessed by a case-control study of people aged 16 years and older who were admitted to 10 Leicestershire hospitals between 1 December 1989 and 31 January 1990. Hospital and general practitioners' records for 156 admissions (the cases) and 289 controls matched for age and sex were reviewed. Information was collected on demography, the usual place of residence (institutional or non-institutional), the existence of chronic illness, and vaccination during the 5 years before admission. The odds ratio for hospital admission among vaccinees was 0.67 (95% CI 0.39-1.12) giving an estimate of vaccine effectiveness in this setting of 33% (95% CI 0-61). However, multivariate logistic regression, adjusting for the effects of institutional care and chronic illness, revealed that influenza vaccination reduced hospital admissions by 63% (95% CI 17-84%). There was a strong trend towards improved vaccine effectiveness when used in institutional settings. Influenza vaccine is effective in reducing hospital admissions for influenza, pneumonia, bronchitis and emphysema, and effectiveness is comparable to that observed for influenza and pneumonia admissions in North America.