Characteristics of Cytomegalovirus Uveitis in Immunocompetent Patients

Woo, Jyh Haur; Lim, Wei‐Wen; Ho, Su Ling; Teoh, Stephen C.

doi:10.3109/09273948.2014.950384

Cited by 51 publications

(39 citation statements)

References 22 publications

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“…Among immunocompromised patients-especially those with an organ transplant, chemotherapy, or AIDS-the reactivation of virus causes life-threatening diseases, such as gastroenteritis, encephalitis, pneumonitis, and graft rejection (5)(6)(7). In addition, HCMV infection is also implicated in widespread ocular damage and potential vision loss from retinitis, anterior uveitis, and corneal endotheliitis (8)(9)(10)(11). Because HCMV infection of the iris is a risk factor during anterior uveitis, understanding the dynamics of viral infection at the molecular level becomes relevant for understanding the viral pathogenesis in general and developing novel strategies to prevent blindness.…”

mentioning

confidence: 99%

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Baldwin

Maus

Zanotti

et al. 2015

J Virol

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H uman cytomegalovirus (HCMV), a member of the betaherpesvirus family, is the leading cause of congenital neurological complications in neonates as a result of maternal infection (1-4). Among immunocompromised patients-especially those with an organ transplant, chemotherapy, or AIDS-the reactivation of virus causes life-threatening diseases, such as gastroenteritis, encephalitis, pneumonitis, and graft rejection (5-7). In addition, HCMV infection is also implicated in widespread ocular damage and potential vision loss from retinitis, anterior uveitis, and corneal endotheliitis (8-11). Because HCMV infection of the iris is a risk factor during anterior uveitis, understanding the dynamics of viral infection at the molecular level becomes relevant for understanding the viral pathogenesis in general and developing novel strategies to prevent blindness. Therefore, we used primary cultures of human iris stromal (HIS) cells as a model to determine the susceptibility and role of 3-O-sulfated heparan sulfate (3-OS HS) during HCMV uveitis.Although HCMV entry into host cells is poorly understood (12, 13), it is clearly a multistep process that requires complex interactions between viral envelope glycoproteins and the host cell receptors (12). It has been suggested that HCMV glycoprotein B (gB) binds to heparan sulfate (HS) during viral attachment, resulting in a high virion concentration at the cell surface and further binding to the cellular receptor (14-17). This interaction has been proposed to modulate immune responses (14, 18). To date, three receptors, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor ␣ (PDGFR␣), and cellular integrins (␣2␤1, ␣6␤1, and ␣v␤3), have been implicated during HCMV entry (19)(20)(21)(22)(23)(24). In addition, recent studies have suggested the potential role of a sulfated form of HS during HCMV entry. For instance, a library of peptides derived from human hemofiltrate and screened for inhibitory effects on HCMV infection implicated the role of 6-O-sulfated HS (6-OS HS) (25) in HCMV entry. Similarly, a peptide generated against 3-OS HS using phage display library screening blocked HCMV entry (26). In addition, several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, and heparin), copolymers of acrylic acid with vinyl alcohol sulfate, and 3-O-sulfated saccharide have proved to be potent inhibitors of HCMV infectivity in vitro (17,27). In this study, we investigated the susceptibility of HIS cells to HCMV infection and the role of 3-OS HS during this process. Our data demonstrate the significance of 3-OS HS during HCMV entry, and we propose a unique in vitro model for future studies related to 3-OS HS-dependent induction of proinflammatory cytokines and virus tropism.Susceptibility of primary cultures of HIS cells to HCMV infection. The HIS cultures were prepared in accordance with institutional review board-approved protocols and were isolated from anonymously donated human eyes (provided by the Illinois Eye Bank, Chicago, IL) via sterile dissecti...

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mentioning

confidence: 99%

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Baldwin

Maus

Zanotti

et al. 2015

J Virol

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show abstract

“…Moreover, additional antibodies specific to herpes simplex virus (8 eyes), cytomegalovirus (2 eyes), and varicella zoster virus (1 eye) were detected in 11 of the eyes with Fuchs heterochromic iridocyclitis (Ruokonen et al, 2010). Another study found that 3 of 16 patients with anterior uveitis and detectable aqueous cytomegalovirus DNA had clinical features consistent with Fuchs heterochromic iridocyclitis (Woo et al, 2014).…”

Section: Ocular Infectionsmentioning

confidence: 93%

Uveitis and glaucoma

Sng

Ang

Barton

2015

Progress in Brain Research

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“…62 It is likely that PCR testing from ocular fluids will become helpful in the diagnosis of a variety of emerging infections causing uveitis, such as chikungunya and West Nile virus. 8 …”

Section: Infectious Uveitismentioning

confidence: 99%

Uveitis

Dunn

2015

Primary Care: Clinics in Office Practice

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Multidisciplinary management in the diagnosis and management of patients with ocular inflammatory disease is often critical. The workup of uveitis or scleritis may reveal an underlying systemic disease. Recognition of inflammation by the primary care physician can facilitate prompt referral to a uveitis specialist and improve patient outcomes. The primary care physician can assist the ophthalmologist in monitoring for potential side effects of corticosteroids and immunosuppressive drugs, including the newer biologic agents. The ophthalmologist in turn can assist the primary care physician in recognizing that active uveitis may suggest incomplete control of preexisting conditions.

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Characteristics of Cytomegalovirus Uveitis in Immunocompetent Patients

Abstract: There is a spectrum of clinical manifestations of CMV anterior uveitis. A high index of suspicion of a possible viral etiology, especially CMV, and subsequent accurate identification of the virus involved are fundamental to the overall therapeutic approach.

Cited by 51 publications

References 22 publications

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

A Role for 3- O -Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells

Uveitis and glaucoma

Uveitis

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