Effect of Host Genetics on the Development of Cytomegalovirus Retinitis in Patients with AIDS

Sezgın, Efe; Jabs, Douglas A.; Hendrickson, Sher L.; Natta, Mark Van; Zdanov, Alexander; Lewis, Richard A.; Smith, Michael W.; Troyer, Jennifer L.; O’Brien, Stephen J.

doi:10.1086/654814

Cited by 37 publications

(30 citation statements)

References 50 publications

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“…Polymorphisms in a limited number of genes, typically related to the immune response, accounted for ~50% of the variability in the time from acquisition of HIV to the development of AIDS in the pre-HAART era and influence the response to HAART 119-121. A collaborative study between the National Cancer Institute Laboratory of Genetic Diversity and the Studies of the Ocular Complications of AIDS Research Group investigated the effect of host genetics on the development of CMV retinitis among patients with AIDS 122. The IL-10 receptor has two subunits (IL-10R1 and IL-10R2), and polymorphisms in the IL-10R1 gene are associated with the development of CMV retinitis in patients with AIDS.…”

Section: Host Factors Affecting Cytomegalovirus Retinitismentioning

confidence: 99%

Cytomegalovirus Retinitis and the Acquired Immunodeficiency Syndrome—Bench to Bedside: LXVII Edward Jackson Memorial Lecture

Jabs

2011

American Journal of Ophthalmology

113

101

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Purpose-To update information on cytomegalovirus (CMV) retinitis in patients with the acquired immune deficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. Design-Literature review.Methods-Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV).Results-Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV retinitis. Systemically-administered treatment for CMV retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART), effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV retinitis. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-ClinicalOff label use of drugs: Discussion of intravitreal injection of antiviral drugs ganciclovir, foscarnet, and cidofovir. NIH Public Access Author ManuscriptAm J Ophthalmol. Author manuscript; available in PMC 2012 February 1.Published in final edited form as: Am J Ophthalmol. 2011 February ; 151(2): 198-216.e1. doi:10.1016/j.ajo.2010.018. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Epidemiology of Cytomegalovirus RetinitisPrior to the advent of the acquired immune deficiency syndrome (AIDS), cytomegalovirus (CMV) retinitis (Figure 1) was a rare disease seen primarily among transplant patients, but also among those with congenital CMV infection and other forms of immune compromise. 1 -4 It was estimated to affect ~1% of patients undergoing renal transplant and ~0.5% of those undergoing bone marr...

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Section: Host Factors Affecting Cytomegalovirus Retinitismentioning

confidence: 99%

Cytomegalovirus Retinitis and the Acquired Immunodeficiency Syndrome—Bench to Bedside: LXVII Edward Jackson Memorial Lecture

Jabs

2011

American Journal of Ophthalmology

113

101

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Section: Host Genetics In CMV Infectionmentioning

confidence: 99%

“…23 CMV contains a human IL-10 homolog gene and utilizes it to evade host immune system. Sezgin et al 23 performed a candidate gene approach by focusing on the polymorphisms in the IL-10R1 and IL-10 genes on the development of CMV retinitis in patients with AIDS. Their results suggest that in European Americans, one haplotype carrying an amino acid changing variation in the cytoplasmic domain of IL-10R1 can be protective against and other haplotype carrying an amino acid changing variation in the extracellular domain of IL-10R1 susceptible to CMV retinitis.…”

Section: Host Genetics In CMV Infectionmentioning

confidence: 99%

“…21,22 Also polymorphisms in genes associated with inflammatory signalling, including IL-10/IL-10R, have been found to be associated with herpesviruses. 23,24 Using murine models, several studies have identified host genetic polymorphisms associated with susceptibility to murine CMV. 25 To obtain more information about the mechanisms of susceptibility to and the strength of anti-CMV immunoglobulin G (IgG) antibody response to CMV infection, we have performed a genome-wide association analysis (GWAS) in a healthy adult population, using serum anti-CMV IgG titer to detect infection.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response

et al. 2011

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Cytomegalovirus (CMV) causes an infection, which is followed by a lifelong latency. CMV has received much attention in clinical studies, but little is known about the genetic basis of this common infection. To identify genetic polymorphisms associated with the susceptibility to and strength of anti-CMV immunoglobulin G (IgG) response to CMV infection, we conducted a genome-wide association study (GWAS) using an Illumina BeadChip containing 670 000 probes and participants from the Cardiovascular Risk in Young Finns Study, including 1486 anti-CMV IgG seropositive and 648 seronegative individuals. Statistical analyses were performed using logistic (for susceptibility) and linear regression (for strength of antibody response). None of single-nucleotide polymorphisms (SNPs) was found to be associated with susceptibility to CMV infection at the level of genome-wide significance (Po5 Â 10 À8). Also, none of the association signals identified reached genome-wide levels of statistical significance in the study of the strength of the antibody response to CMV although five SNPs in AGBL1 gene region displayed a suggestive association (lowest P-value ¼ 1.86 Â 10 À6 ). The results indicate that there is no strong evidence of major host genetic factors involved in either susceptibility to or the strength of antibody response to human CMV infection.

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“…Among African Americans, a promoter haplotype within C-C chemokine receptor type 5 (CCR5) and a polymorphism in the stromal cell-derived factor 1 (SDF1) were associated with increased risk of retinitis progression [5,6]. In white patients, different haplotypes of the interleukin (IL)-10 receptor subunit 1 (IL10-R1) [5] and polymorphisms within tumor necrosis factor (TNF) [7] were linked to susceptibility to CMV retinitis. Interferon-lambda 3 (IFNL3) (previously designated as IL28B) belongs to the type III IFN family and was reported as a major determinant of hepatitis C virus (HCV) clearance.…”

Section: Introductionmentioning

confidence: 99%

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients

Bibert¹,

Wójtowicz²,

Taffé³

et al. 2014

Aids

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Effect of Host Genetics on the Development of Cytomegalovirus Retinitis in Patients with AIDS

Cited by 37 publications

References 50 publications

Cytomegalovirus Retinitis and the Acquired Immunodeficiency Syndrome—Bench to Bedside: LXVII Edward Jackson Memorial Lecture

Cytomegalovirus Retinitis and the Acquired Immunodeficiency Syndrome—Bench to Bedside: LXVII Edward Jackson Memorial Lecture

Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients

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