Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway

Hooks, John J.; Chin, Michael C.; Srinivasan, K.; Momma, Yuko; Hooper, Laura C.; Nagineni, Chandrasekharam N.; Chan, Chi Chao; Detrick, Barbara

doi:10.1016/j.micinf.2006.04.010

Cited by 32 publications

(20 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of infected cells with ISIS 2922 (vitravine), an antisense oligonucleotide to the HCMV immediate-early transcriptional unit, abrogated COX-2 mRNA expression and PGE 2 synthesis. These results confirm HCMV specifically induces higher COX-2 levels and increased synthesis of PGE 2 in human RPE, providing insight into the pathophysiology and treatment of HCMVinduced retinitis most prevalently diagnosed in immunocompromised individuals [48].…”

Section: Introductionsupporting

confidence: 69%

“…Immunohistochemical analysis of ocular tissue sections from AIDS patients diagnosed with HCMV-induced retinitis revealed increased levels of COX-2 protein specifically within HCMV antigen-positive human retinal pigment epithelial cells (RPE) [48]. By day 5 post-infection, wild-type HCMV infected primary RPE cultures exhibited increased levels of viral transcripts (HCMV IE72, IE86 and pp65) with concomitant elevation of COX-2 transcripts, COX-2 protein levels and COX activity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biological interactions between herpesviruses and cyclooxygenase enzymes

Reynolds

Enquist

2006

Reviews in Medical Virology

View full text Add to dashboard Cite

Decades ago, medical researchers noted that non-steroidal anti-inflammatory drugs (NSAIDs), for example aspirin and indomethacin, modulate primary herpesvirus infections and diminish reactivation of latent herpesvirus infections. NSAIDs inhibit cyclooxygenase (COX) enzymes, molecules necessary for generation of prostaglandins. Numerous studies indicate that herpesvirus infections elicit elevated levels of cyclooxygenase 2 (COX-2) with a resultant increase in prostaglandin E(2) levels (PGE(2)). Thus, the biochemical pathway underlying the anti-herpetic mechanism of NSAIDs is linked to the inhibition of COX. The precise roles of COX-2 and PGE(2) in the viral life cycle are unknown. However, among the alphaherpesvirus, betaherpesvirus and gammaherpesvirus subfamilies, evolutionarily conserved mechanisms ensure modulated expression of COX molecules, underscoring their importance in viral replication and virus-host interactions.

show abstract

Section: Introductionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Biological interactions between herpesviruses and cyclooxygenase enzymes

Reynolds

Enquist

2006

Reviews in Medical Virology

View full text Add to dashboard Cite

show abstract

“…One characterized gene is Rh10 (vCOX-2), a viral homologue to the gene for the host cyclooxygenase-2 enzyme (COX-2), which is a member of the eicosanoid synthetic pathway. Unlike HCMV (35,79,82), RhCMV does not induce cellular COX-2 expression, suggesting that the virus encodes its own copy of the protein to compensate for this lack. vCox-2 was shown to facilitate growth in endothelial cells (65).…”

Section: Resultsmentioning

confidence: 99%

Reevaluation of the Coding Potential and Proteomic Analysis of the BAC-Derived Rhesus Cytomegalovirus Strain 68-1

Malouli

Nakayasu

Viswanathan

et al. 2012

J Virol

View full text Add to dashboard Cite

Cytomegaloviruses are highly host restricted, resulting in cospeciation with their hosts. As a natural pathogen of rhesus macaques (RM), rhesus cytomegalovirus (RhCMV) has therefore emerged as a highly relevant experimental model for pathogenesis and vaccine development due to its close evolutionary relationship to human CMV (HCMV). Most in vivo experiments performed with RhCMV employed strain 68-1 cloned as a bacterial artificial chromosome (BAC). However, the complete genome sequence of the 68-1 BAC has not been determined. Furthermore, the gene content of the RhCMV genome is unknown, and previous open reading frame (ORF) predictions relied solely on uninterrupted ORFs with an arbitrary cutoff of 300 bp. To obtain a more precise picture of the actual proteins encoded by the most commonly used molecular clone of RhCMV, we reevaluated the RhCMV 68-1 BAC genome by whole-genome shotgun sequencing and determined the protein content of the resulting RhCMV virions by proteomics. By comparing the RhCMV genome to those of several related Old World monkey (OWM) CMVs, we were able to filter out many unlikely ORFs and obtain a simplified map of the RhCMV genome. This comparative genomics analysis suggests a high degree of ORF conservation among OWM CMVs, thus decreasing the likelihood that ORFs found only in RhCMV comprise true genes. Moreover, virion proteomics independently validated the revised ORF predictions, since only proteins that were conserved across OWM CMVs could be detected. Taken together, these data suggest a much higher conservation of genome and virion structure between CMVs of humans, apes, and OWMs than previously assumed.

show abstract

“…The cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 ) pathway is one of several host pathways that participate in the modulation of the host response to the infection and the replicative life cycle of viruses (7). For example, the activation of the COX-2/PGE 2 pathway results in increased replication of cytomegalovirus (8, 9), but PGE 2 inhibits the replication of parainfluenza 3 virus and adenovirus (10, 11). COXs convert arachidonic acid released by phospholipase A2- and C-mediated hydrolysis of plasma membrane phospholipids following exposure to diverse physiological and pathological stimuli into prostaglandins (PGs), prostacyclins, and thromboxanes (12, 13).…”

Section: Introductionmentioning

confidence: 99%

Activation of COX-2/PGE ₂ Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production

Alfajaro

Choi

Kim

et al. 2017

J Virol

View full text Add to dashboard Cite

Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection.IMPORTANCE Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting of COX-1/2 using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We further demonstrate that the production of PGE2 provides a protective effect against the antiviral effector mechanism of nitric oxide. Our findings uncover a new mechanism by which PSaV manipulates the host cell to provide an environment suitable for efficient viral growth, which in turn can be a new target for treatment of sapovirus infection.

show abstract

Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway

Cited by 32 publications

References 26 publications

Biological interactions between herpesviruses and cyclooxygenase enzymes

Biological interactions between herpesviruses and cyclooxygenase enzymes

Reevaluation of the Coding Potential and Proteomic Analysis of the BAC-Derived Rhesus Cytomegalovirus Strain 68-1

Activation of COX-2/PGE ₂ Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production

Contact Info

Product

Resources

About

Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway

Cited by 32 publications

References 26 publications

Biological interactions between herpesviruses and cyclooxygenase enzymes

Biological interactions between herpesviruses and cyclooxygenase enzymes

Reevaluation of the Coding Potential and Proteomic Analysis of the BAC-Derived Rhesus Cytomegalovirus Strain 68-1

Activation of COX-2/PGE 2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production

Contact Info

Product

Resources

About

Activation of COX-2/PGE ₂ Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production