Rhinovirus Replication Research Articles

Does isoflurane enhance rhinovirus replication and virus‐induced cytokine secretion in airway epithelial cells?

There have been no previous studies regarding the effect of volatile anesthetics on human rhinovirus (RV) infection in airway epithelial cells of patients with an upper respiratory infection (URI). We have therefore evaluated in vitro the effect of isoflurane on RV infection in airway epithelial cells. A549 cells and RV-infected A549 cells were treated with isoflurane for 2 or 4 h. Surface expression of intercellular adhesion molecule-1 (ICAM-1) was assessed by flow cytometry, and effects on the secretion of interleukin (IL)-6 and IL-8 were measured by ELISA. The effect on RV replication in the cells was determined by viral titer. Isoflurane treatment for 2 or 4 h had no significant effect on ICAM-1 expression and secretion of IL-6 and IL-8 in control cells. Isoflurane also had no significant additional effect on RV-induced ICAM-1 expression and secretion of IL-6 and IL-8. Viral titers were not significantly influenced by isoflurane. Isoflurane treatment showed no additional effects with RV on ICAM-1 expression, secretion of IL-6 and IL-8, and viral titer in A549 cells. These results suggest that isoflurane itself may not increase further RV infections, inflammations, and viral replication in patients with a viral URI.

Rhinovirus infections in infants: is respiratory syncytial virus ready for the challenge?

Human rhinoviruses are the leading cause of upper respiratory tract infections ( i.e. the common cold) in both adults and children 1. On average, adults experience one rhinovirus infection each year, whereas, in young children, it is a more frequent occurrence. Although rhinovirus infections are limited to the common cold in most cases, they are also a frequent cause of acute sinusitis and otitis media (subsequently leading to antibiotic overuse). Rhinovirus tropism and replication, however, is not limited to the upper respiratory tract. It has been recognised that rhinoviruses can replicate in the lower respiratory tract and lead to lower respiratory tract illnesses, particularly in the elderly, in immunocompromised patients and in children. It is has also been established that rhinoviruses contribute to the majority of asthma exacerbations in both adults and children, and to nearly half of all chronic obstructive pulmonary disease (COPD) exacerbations. Given the technical difficulties involved in isolating rhinovirus in cell cultures, it has only been in recent years, with the advent of viral genome detection via RT-PCR, that a clearer understanding of the impact of these infections has emerged 2. In infants, acute viral respiratory illnesses are the major cause of morbidity and mortality. Several recent community-based studies of infants at high risk of atopy or those attending day care have consistently found rhinoviruses to be the most frequent viruses associated with acute respiratory infections or wheezing illnesses 3–5. The leading role of rhinoviruses in infancy was recently corroborated in a birth cohort study of otherwise healthy infants, who were studied at the first acute respiratory infection with cough or wheeze 6. In addition, the potential severity of rhinovirus-associated diseases has been demonstrated by case series describing bronchiolitis, pneumonia and …

Gene Expression Profiles duringIn VivoHuman Rhinovirus Infection

Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases. To define changes in gene expression profiles during in vivo rhinovirus infections. Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections. Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells. Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.

Anti-inflammatory effects of long-chainn-3 PUFA in rhinovirus-infected cultured airway epithelial cells

Long-chain n-3 PUFA (LCn-3PUFA) including DHA and EPA, are known to decrease inflammation by inhibiting arachidonic acid (AA) metabolism to eicosanoids, decreasing the production of pro-inflammatory cytokines and reducing immune cell function. The aim of this study was to determine if EPA and DHA reduced the release of inflammatory mediators from airway epithelial cells infected with rhinovirus (RV). Airway epithelial cells (Calu-3) were incubated with EPA, DHA and AA for 24 h, followed by rhinovirus infection for 48 h. IL-6, IL-8 and interferon-gamma-induced protein-10 (IP-10) released by cells were measured using ELISA. Viral replication was measured by serial titration assays. The fatty acid content of cells was analysed using GC. Cellular viability was determined by visual inspection of cells and lactate dehydrogenase release. DHA (400 microm) resulted in a significant 16% reduction in IL-6 release after RV-43 infection, 29% reduction in IL-6 release after RV-1B infection, 28% reduction in IP-10 release after RV-43 infection and 23 % reduction in IP-10 release after RV-1B infection. Cellular DHA content negatively correlated with IL-6 and IP-10 release. None of the fatty acids significantly modified rhinovirus replication. DHA supplementation resulted in increased cellular content of DHA at the cost of AA, which may explain the decreased inflammatory response of cells. EPA and AA did not change the release of inflammatory biomarkers significantly. It is concluded that DHA has a potential role in suppressing RV-induced airway inflammation.

Inhibition of Human Rhinovirus Replication by Some Antivirals

Inhibition of Human Rhinovirus Replication by Some Antivirals

Effect of propofol and etomidate in respiratory epithelial cell infected with rhinovirus

Background: There have been no previous studies on the effect of anesthetic agents on rhinovirus (RV) infection, which is the most common pathogen of the common cold in human airway epithelial cells. We investigated the effects of propofol and etomidate on the airway epithelial cells infected with RV. Methods: RV-infected A549 cells were treated with propofol and etomidate for 24 hours. On the third day of infection, cells and supernatant were collected to measure the intercellular adhesion molecule-1 (ICAM-1) expression, viral titer and the amount of cytokine. The extents of the viral replication were expressed as viral titers by 50% tissue culture infection dose (TCID50). Results: The ICAM-1 expression of the groups treated with propofol 1, 10, 100μM vs etomidate 1, 5, 25μM were 15.6 ± 4.2, 16.4 ± 3.7, 14.1 ± 4.7% vs 16.8 ± 5.7, 16.4 ± 5.3, 17.2 ± 4.5%, but there were not significantly different among subgroups. Productions of cytokines were increased after RV-infection, but there were not significantly different among the propofol and etomidate treated subgroups. The viral titers of the groups treated with propofol and etomidate were not significantly different among subgroups either. Conclusions: Propofol and etomidate had no effect on the replication of RV and the cytokine release after RV infection in human airway epithelial cells.

Staphylococcal Enterotoxins A and B Enhance Rhinovirus Replication in A549 Cells

Staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) have been reported to be important in the pathogenesis of chronic rhinosinusitis (CRS). To elucidate the pathophysiological responses in the nasal mucosae of CRS patients associated with rhinovirus (RV) infection, we investigated the effects of SEA and SEB on RV infection in A549 cells. Changes in expression of intercellular adhesion molecule (ICAM) 1 were assessed by flow cytometry, and effects on cytokine secretion were measured by ELISA. The changes of ICAM-1, IL-1beta, IL-6, and IL-8 mRNA were assayed by real-time polymerase chain reaction. The effect of RV replication in the cells was assessed by viral culture, followed by determination of viral titer. RV infection increased ICAM-1 expression and cytokine secretion, but the SEs did not further increase the RV-induced expression of ICAM-1, IL-1beta, IL-6, and IL-8 mRNA and protein. The SEs, however, induced dose-dependent increases in viral titer. SEA and SEB enhanced rhinoviral replication in airway epithelial cells, indicating that airway epithelial cells with CRS are more favorable environments for RV infection.

Inhibition of Rhinovirus Replication In Vitro and In Vivo by Acid‐Buffered Saline

Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus. Preliminary experiments verified that the surface pH of the human nasopharynx could be transiently lowered to pH ∼4.0 by topical administration of citrate/phosphate (CP) buffers, which was well tolerated. In a pilot experimental colds study, intranasal administration of CP buffer, compared with normal saline, reduced viral shedding by 1 log unit (103 vs. 104 50%tissue culture infective dose/mL; P < .01), although respiratory symptoms were not significantly reduced. These findings demonstrate that low-pH buffers have antiviral activity in vivo and suggest that a larger clinical trial is warranted to determine whether this approach could reduce rates of viral transmission.

PDTC inhibits picornavirus polyprotein processing and RNA replication by transporting zinc ions into cells

Previously, it was shown that pyrrolidine dithiocarbamate (PDTC) inhibits proteolytic polyprotein processing and replication of human rhinovirus by transporting metal ions into cells. Here, it is shown that PDTC also inhibits replication of two other picornaviruses: coxsackievirus B3 (CVB3), a closely related virus that belongs to the genus Enterovirus, and mengovirus, an encephalomyocarditis virus strain that belongs to the genus Cardiovirus, and that this inhibition is due to the dithiocarbamate moiety of the compound. Making use of subgenomic replicons, evidence is provided that PDTC inhibits replication of these two viruses by disturbing viral RNA synthesis. Furthermore, it is shown that PDTC transports zinc ions into cells and that these zinc ions play an important role in the antiviral activity mediated by PDTC. Finally, it is shown that PDTC interferes with proteolytic processing of the polyproteins of both CVB3 and mengovirus, but that the underlying mechanism between these two viruses differs. In CVB3-infected cells, PDTC interferes strongly with the proteolytic activity of 3CD(pro), as shown by the impaired production of the mature capsid proteins as well as the autocleavage of 3CD(pro) into 3C(pro) and 3D(pol). In mengovirus-infected cells, however, PDTC had no effect on the proteolytic production of capsid proteins or the autocleavage of 3CD(pro). Instead, PDTC caused the accumulation of a high-molecular-mass precursor protein, due to an impairment in the primary 'break' that normally occurs at the 2A-2B junction. Thus, PDTC disturbs polyprotein processing and replication of two groups of picornaviruses, enteroviruses and cardioviruses, but the underlying mechanism is different.

Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance

The genome diversity of RNA viruses allows for rapid adaptation to a wide variety of adverse conditions. Accordingly, viruses can escape inhibition by most antiviral compounds targeting either viral or host factors. Here we exploited the capacity of RNA viruses for rapid adaptation to explore the evolutionary constraints of chaperone-mediated protein folding. We hypothesized that inhibiting a host molecular chaperone required for folding of a viral protein would force the virus to evolve an alternate folding strategy. We identified the chaperone Hsp90 as an essential factor for folding and maturation of picornavirus capsid proteins. Pharmacological inhibition of Hsp90 impaired the replication of poliovirus, rhinovirus, and coxsackievirus in cell culture. Strikingly, anti-Hsp90 treatment did not yield drug-resistant viruses, suggesting that the complexity of capsid folding precludes the emergence of alternate folding pathways. These results reveal tight evolutionary constraints on chaperone-mediated protein folding, which may be exploited for viral inhibition in vivo. Indeed, Hsp90 inhibitors drastically reduced poliovirus replication in infected animals without the emergence of drug-resistant escape mutants. We propose that targeting folding of viral proteins may provide a general antiviral strategy that is refractory to development of drug resistance.

How Viral Infections Cause Exacerbation of Airway Diseases

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

Protein kinase R, IκB kinase-β and NF-κB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells

Rhinovirus infections cause the majority of acute exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease, with increased pro-inflammatory cytokine production by infected bronchial epithelial cells contributing to disease pathogenesis. Theses diseases are a huge cause of morbidity worldwide, and contribute a major economic burden to healthcare costs. Current steroid based treatments are only partially efficient at controlling virus induced inflammation, which remains an unmet therapeutic goal. Although NF-κB has been implicated, the precise mechanisms of rhinovirus induction of pro-inflammatory gene expression in bronchial epithelial cells are unclear. We hypothesised that rhinovirus replication and generation of dsRNA was an important process of pro-inflammatory cytokine induction. Using pharmalogical (2-aminopurine and a new small molecule inhibitor) and genetic inhibition of the dsRNA binding kinase protein kinase R, striking inhibition of dsRNA (polyrIC) and rhinovirus induced CCL5, CXCL8 and IL-6 protein was observed. Using confocal microscopy, rhinovirus induced protein kinase R phosphorylation co-located with NF-κB p65 nuclear translocation. Focusing on CXCL8, both rhinovirus infection and dsRNA treatment required IκB kinase-β for induction of CXCL8. Analysis of cis-acting sites in the CXCL8 promoter revealed that both rhinovirus infection and dsRNA treatment upregulated CXCL8 promoter activation via NF-κB and NF-IL6 binding sites. Together, the results demonstrate the importance of dsRNA in induction of pro-inflammatory cytokines by rhinoviruses, and suggest that protein kinase R is involved in NF-κB mediated gene transcription of pro-inflammatory cytokines via IκB kinase-β. These molecules regulating rhinovirus induction of inflammation represent therapeutic targets.

Rhinovirus Replication in Human Macrophages Induces NF-κB-Dependent Tumor Necrosis Factor Alpha Production

Rhinoviruses (RV) are the major cause of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Rhinoviruses have been shown to activate macrophages, but rhinovirus replication in macrophages has not been reported. Tumor necrosis factor alpha (TNF-alpha) is implicated in the pathogenesis of acute exacerbations, but its cellular source and mechanisms of induction by virus infection are unclear. We hypothesized that rhinovirus replication in human macrophages causes activation and nuclear translocation of NF-kappaB, leading to TNF-alpha production. Using macrophages derived from the human monocytic cell line THP-1 and from primary human monocytes, we demonstrated that rhinovirus replication was productive in THP-1 macrophages, leading to release of infectious virus into supernatants, but was limited in monocyte-derived macrophages, likely due to type I interferon production, which was robust in monocyte-derived but deficient in THP-1-derived macrophages. Similar to bronchial epithelial cells, only small numbers of cells supported complete virus replication. We demonstrated RV-induced activation of NF-kappaB and colocalization of p65/NF-kappaB nuclear translocation with virus replication in both macrophage types. The infection induced TNF-alpha release in a time- and dose-dependent, RV serotype- and receptor-independent manner and was largely (THP-1 derived) or completely (monocyte derived) dependent upon virus replication. Finally, we established the requirement for NF-kappaB but not p38 mitogen-activated protein kinase in induction of TNF-alpha. These data suggest RV infection of macrophages may be an important source of proinflammatory cytokines implicated in the pathogenesis of exacerbations of asthma and COPD. They also confirm inhibition of NF-kappaB as a promising target for development of new therapeutic intervention strategies.

S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells during the human immune response to rhinovirus

Human rhinovirus infection is a common trigger for asthma exacerbations. Asthma exacerbations and rhinovirus infections are both associated with markedly decreased pH and ammonium levels in exhaled breath condensates. This observation is thought to be related, in part, to decreased activity of airway epithelial glutaminase. We studied whether direct rhinovirus infection and/or the host immune response to the infection decreased airway epithelial cell surface pH in vitro. Interferon-gamma and tumor necrosis factor-alpha, but not direct rhinovirus infection, decreased pH, an effect partly associated with decreased ammonium concentrations. This effect was 1) prevented by nitric oxide synthase inhibition; 2) independent of cyclic GMP; 3) associated with an increase in endogenous airway epithelial cell S-nitrosothiol concentration; 4) mimicked by the exogenous S-nitrosothiol, S-nitroso-N-acetyl cysteine; and 5) independent of glutaminase expression and activity. We then confirmed that decreased epithelial pH inhibits human rhinovirus replication in airway epithelial cells. These data suggest that a nitric oxide synthase-dependent host response to viral infection mediated by S-nitrosothiols, rather than direct infection itself, plays a role in decreased airway surface pH during human rhinovirus infection. This host immune response may serve to protect the lower airways from direct infection in the normal host. In patients with asthma, however, this fall in pH could be associated with the increased mucus production, augmented inflammatory cell degranulation, bronchoconstriction, and cough characteristic of an asthma exacerbation.

Inhibition of Polyprotein Processing and RNA Replication of Human Rhinovirus by Pyrrolidine Dithiocarbamate Involves Metal Ions

Pyrrolidine dithiocarbamate (PDTC) is an antiviral compound that was shown to inhibit the replication of human rhinoviruses (HRVs), poliovirus, and influenza virus. To elucidate the mechanism of PDTC, the effects on the individual steps of the infection cycle of HRV were investigated. PDTC did not interfere with receptor binding or internalization by receptor mediated endocytosis of HRV2 particles into HeLa cells. But we demonstrate that the processing of the viral polyprotein was prevented by PDTC treatment in HeLa cells infected with HRV2. Furthermore, PDTC inhibited the replication of the viral RNA, even when added four hours post infection. As PDTC is described as a metal ion binding agent, we investigated the effect of other metal chelators on the multiplication of HRV2. We show that EDTA, omicron-phenanthroline, and bathocuproine disulfonic acid do not exhibit any antiviral properties. Surprisingly, these substances, coadministered with PDTC, abolished the antiviral effect of PDTC, suggesting that metal ions play a pivotal role in the inhibition of virus multiplication. These results suggest that PDTC inhibits the activity of the viral proteases in a metal ion dependent way.

Pyrrolidine Dithiocarbamate Reduces Coxsackievirus B3 Replication through Inhibition of the Ubiquitin-Proteasome Pathway

Coxsackievirus B3 (CVB3) is one of the most common pathogens for viral myocarditis. The lack of effective therapeutics for CVB3-caused viral diseases underscores the importance of searching for antiviral compounds. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and is recently reported to inhibit ubiquitin-proteasome-mediated proteolysis. Previous studies have shown that PDTC inhibits replication of rhinovirus, influenza virus, and poliovirus. In the present study, we report that PDTC is a potent inhibitor of CVB3. Coxsackievirus-infected HeLa cells treated with PDTC showed a significant reduction of CVB3 viral RNA synthesis, viral protein VP1 expression, and viral progeny release. Similar to previous observation that divalent ions mediate the function of PDTC, we further report that serum-containing copper and zinc are required for its antiviral activity. CVB3 infection resulted in massive generation of reactive oxygen species (ROS). Although PDTC alleviated ROS generation, the antiviral activity was unlikely dependent on its antioxidant effect because the potent antioxidant, N-acetyl-L-cysteine, failed to inhibit CVB3 replication. Consistent with previous reports that PDTC inhibits ubiquitin-proteasome-mediated protein degradation, we found that PDTC treatment led to the accumulation of several short-lived proteins in infected cells. We further provide evidence that the inhibitory effect of PDTC on protein degradation was not due to inhibition of proteasome activity but likely modulation of ubiquitination. Together with our previous findings that proteasome inhibition reduces CVB3 replication (H. Luo, J. Zhang, C. Cheung, A. Suarez, B. M. McManus, and D. Yang, Am. J. Pathol. 163:381-385, 2003), results in this study suggest a strong antiviral effect of PDTC on coxsackievirus, likely through inhibition of the ubiquitin-proteasome pathway.

Proteolytic Cleavage of the p65-RelA Subunit of NF-κB during Poliovirus Infection

Activation of NF-kappaB during viral infection is one of the critical elements in innate immune response. Several virus-specific factors, such as double-stranded RNA, can trigger host defense mechanisms by inducing NF-kappaB-mediated expression of cytokines and interferons. Early stages of poliovirus infection are also associated with degradation of IkappaB alpha and translocation of NF-kappaB into the nucleus. However, at later stages of poliovirus replication the p65-RelA component of the NF-kappaB complex undergoes a specific cleavage that coincides with the onset of intensive poliovirus protein synthesis and the appearance of the activity of poliovirus protease 3C. Indeed, the p65-RelA amino acid sequence contains the recognition site for 3C, and recombinant protein 3C was shown to be capable of proteolytic cleavage of p65-RelA, generating truncated product similar to that observed during poliovirus infection. Cleavage of p65-RelA occurs during replication of ECHO-1 and rhinovirus 14, suggesting that inactivation of NF-kappaB function by proteolytic cleavage of p65-RelA is the common mechanism by which picornaviruses suppress the innate immune response.

Hydroxychloroquine (HCQ) inhibits rhinovirus (RV) replication in cultured human tracheal epithelial cells

Rationale The immunomodulating agent, HCQ, inhibits transmission of respiratory viruses adenovirus and influenza, which require acidified cytoplasmic vesicles for cellular entry. Based on an apparent low incidence of symptomatic upper respiratory tract infections in asthmatics treated with oral HCQ, we hypothesized that HCQ might inhibit RV infection in respiratory epithelial cells. Methods Differentiated cultures of human tracheal epithelial cells grown at an air liquid interface were pre-incubated for 12h with 50 μM HCQ prior to 12h infection with RV serotype 16. Twelve hours after removal of virus, numbers of infected cells were measured using confocal Immunofluorescence microscopy. Levels of mRNA for RV were quantified using multiplex two-step RT-PCR. Release of IL-8 was measured by ELISA. Results Small numbers of cells positive for RV-16 in control cultures were significantly increased by RV-16 infection, an effect substantially blocked by HCQ (see Table). Furthermore, HCQ reduced levels of viral mRNA in infected cells by 32-fold. Viral infection was also associated with increased output of IL-8 into both apical and basolateral media, and again HCQ inhibited this (see Table). ∗ Condition % Infected Cells IL-8 production (pg.cm −3.h −1) Control 0.12 ± 0.1 203 ± 26 RV16 4.36 ± 0.94 96 ± 37 RV16 + HCQ 1.01 ± 0.21 ∗ 339 ± 46 ∗ ∗ Significantly less than with virus alone. Conclusions These findings demonstrate potent in vitro inhibition of RV infection by HCQ and suggest that targeted topical delivery of HCQ to the respiratory epithelium may offer a novel strategy for prevention of RV infections.

Effects of inflammatory cytokines on the permeability of human lung microvascular endothelial cell monolayers and differential eosinophil transmigration

Background: Rhinovirus (RV) infections can result in asthma exacerbations in both adults and children. Respiratory epithelium, the primary site of RV replication, responds to the viral infection by generating a variety of cytokines and chemokines capable of promoting airway inflammation and hence might increase asthma severity. Some of these mediators might also affect the permeability of underlying vascular endothelium. Objective: We hypothesized that RV infections can promote airway inflammation and thus asthma by enhancing local vascular permeability. Methods: Confluent human lung microvascular endothelial cell (HMVEC-L) monolayers were used as an in vitro model of vascular endothelium to determine whether cytokines associated with RV-induced infections are capable of modulating endothelial cell permeability as measured by means of transendothelial electrical resistance. Recombinant cytokines and chemokines were added to confluent HMVEC-L monolayers cultured on Transwell filters, and permeability was measured as decreased electrical resistance over time. Eosinophil transendothelial migration was assessed under the same experimental conditions. Results: TNF- α, IL-1 β, and IFN- γsignificantly increased HMVEC-L permeability. In contrast, GM-CSF, G-CSF, IL-8, IL-6, and RANTES had no effect. Although incubation of HMVEC-L monolayers with either TNF-α or IL-1β promoted eosinophil migration, IFN-γ had no effect, indicating that enhanced permeability alone was not sufficient for eosinophil infiltration. Conclusion: Select cytokines, generated in response to RV infection, can increase vascular permeability and might provide a mechanism by which RV infection can lead to edema, cellular infiltration, and inflammation and thus compromised airflow. (J Allergy Clin Immunol 2002;110:752-6.)

ChemInform Abstract: Three‐Dimensional Quantitative Structure—Permeability Relationship Analysis for a Series of Inhibitors of Rhinovirus Replication.

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