Retinal Detachment Associated With AIDS-Related Cytomegalovirus Retinitis: Risk Factors in a Resource-Limited Setting

Yen, Michael T.; Chen, Jenny; Kunavisarut, Paradee; Vichitvejpaisal, Pornpattana; Ausayakhun, Somsanguan; Jirawison, Choeng; Shantha, Jessica G.; Holland, Gary N.; Heiden, David; Margolis, Todd P.; Keenan, Jeremy D.

doi:10.1016/j.ajo.2014.10.014

Cited by 22 publications

(10 citation statements)

References 43 publications

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“…Although in immunocompetent individuals HCMV infection is typically asymptomatic, in the case of congenital infection, the virus can cause severe neurological sequelae such as deafness and developmental defects following infection of the fetus (Grosse, Ross, and Dollard, 2008; Johnson and Anderson, 2014). In immunocompromised individuals, including those with HIV/AIDS or those receiving organ transplants, HCMV can cause devastating morbidity and mortality including pneumonia, retinitis, and transplant rejection (Ljungman, Hakki, and Boeckh, 2011; Paya et al, 2004; Yen et al, 2015). Moreover, many studies have shown that HCMV can be associated with chronic diseases such as atherosclerosis and hypertension, cancer, and autoimmune disease (Dziurzynski et al, 2012; Li et al, 2011; Streblow, Orloff, and Nelson, 2001; Varani et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line

Miller

2015

Virology

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Human cytomegalovirus (HCMV) resides in a latent form in hematopoietic progenitors and undifferentiated cells within the myeloid lineage. Maturation and differentiation along the myeloid lineage triggers lytic replication. Here, we used peripheral blood monocytes and the monocytic cell line THP-1 to investigate the effects of 1,25-dihydroxyvitamin D3 on HCMV replication. Interestingly, 1,25-dihydroxyvitamin D3 induces lytic replication marked by upregulation of HCMV gene expression and production of infectious virus. Moreover, we demonstrate that the effects of 1,25-dihydroxyvitamin D3 correlate with maturation/differentiation of the monocytes and not by directly stimulating the MIEP. These results are somewhat surprising as 1,25-dihydroxyvitamin D3 typically boosts immunity to bacteria and viruses rather than driving the infectious life cycle as it does for HCMV. Defining the signaling pathways kindled by 1,25-dihydroxyvitamin D3 will lead to a better understanding of the underlying molecular mechanisms that determine the fate of HCMV once it infects cells in the myeloid lineage.

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Section: Introductionmentioning

confidence: 99%

The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line

Miller

2015

Virology

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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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“…[14] A further study looked at risk factors for developing retinal detachments in patients with CMV retinitis and found bilateral disease and lesion size to be the strongest predictors. [15] Our study failed to demonstrate an association between the number of retinal quadrants involved and retinal detachment, but we did not specifically measure lesion size. Prophylactic argon retinal photocoagulation has been successful in anecdotal reports and small case series, [16] but there is no uniformity among the centres in SA with regard to treating patients prophylactically with laser.…”

Section: Discussionmentioning

confidence: 77%

Cytomegalovirus retinitis in Cape Town, South Africa: Clinical management and outcomes

Lapere

Rice

2017

S Afr Med J

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Background. Cytomegalovirus (CMV) retinitis is a vision-threatening opportunistic infection that occurs mainly in immunocompromised individuals. Limited data on treatment protocols and management outcomes are available in South Africa (SA). Objectives. To review the clinical presentation, management and outcomes of patients who were diagnosed and treated for CMV retinitis at Groote Schuur Hospital, Cape Town, SA, over a 10-year period, and to compare treatment protocols of 13 public hospitals in SA that treat patients for CMV retinitis. Methods. A retrospective case review was performed of all patients treated for CMV retinitis at Groote Schuur Hospital between 2003 and 2013. In addition, a questionnaire was sent to 13 public hospitals in SA that treat patients with CMV retinitis. Results. A total of 141 eyes in 91 patients were polymerase chain reaction-positive for CMV. Of these patients, 98.6% were HIV-positive and 72.5% were on highly active antiretroviral therapy (HAART) at the time of presentation. Patients who were on HAART at presentation had better mean final visual acuity (VA) than those who were not on HAART (p<0.001). There was a significant association between the number of retinal quadrants involved and final visual outcome (p=0.009). Macular (central vision) involvement had a significant adverse effect on visual outcome compared with cases in which the macula was uninvolved (p=0.005). Conclusions. Independent risk factors that predict final visual outcome include presenting VA, number of retinal quadrants involved, macular involvement and being on HAART at presentation. The diagnosis and management of CMV retinitis differ among treatment centres in SA.

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Retinal Detachment Associated With AIDS-Related Cytomegalovirus Retinitis: Risk Factors in a Resource-Limited Setting

Cited by 22 publications

References 43 publications

The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line

The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in peripheral blood monocytes and in the THP-1 monocytic cell line

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

Cytomegalovirus retinitis in Cape Town, South Africa: Clinical management and outcomes

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