Robertson, Erle S
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Publication Multiple Oncogenic Viruses Identified in Ocular Surface Squamous Neoplasia in HIV-1 Patients(2010-03-26) Simbiri, Kenneth O; Feldman, Michael; Steenhoff, Andrew P; Bisson, Gregory P; Murakami, Masanao; Robertson, Erle S; Nkomazana, OathokwaBackground Ocular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. Results Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples. Conclusion We identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN.Publication Characterization of the OSSN Microbiome in HIV-1 Infected Patients(2012-05-01) Simbiri, Kenneth O; Robertson, Erle SPurpose: Ocular surface squamous neoplasia (OSSN) is a rare cancer previously seen in elderly men. In Botswana there is an increase in OSSN and pterygia among young HIV-1 infected patients. Factors that determine the course of this cancer have not been characterized. Recent studies identified HPV, EBV, KSHV, HSV-1/2, and CMV in patient samples. We now characterize the microbiome associated with the disease that may contribute to its course. Results: Pyrosequencing identified viruses, bacteria, fungus and parasites. Analysis of shotgun cloning sequences showed a majority of infectious agents identified by pyrosequencing. Conclusion: HIV patients with OSSN in Botswana are infected with a range of infectious agents which may represent a unique microbiome. The persistent expressions of gene products by these agents some of which are oncogenic are likely to contribute to the oncogenic process and suggest that treatment modalities of the cancer should involve the screening for endemic agents.Publication Cytokine and Chemokine Expression Profiles in HIV-1 Infected Patients With Ocular Surface Squamous Neoplasia From Botswana(2012-05-28) Simbiri, Kenneth O; Jha, Hem C; Robertson, Erle S; Dzeng, Richard K; Massaro-Giordano, GiacominaPurpose: Ocular surface squamous neoplasia (OSSN) rate has increased in incidence with the HIV pandemic in Africa. Multiple factors including cellular and environmental can affect the pathogenesis of OSSN in HIV-infected patients. We will investigate anti-inflammatory cytokines, proinflammatory cytokines, and growth factor expression in sera and tissue samples of OSSN and pterygia for the potential link to the development of OSSN. Results: Antibody analysis showed significant changes in levels of pro-inflammatory cytokines, anti-inflammatory cytokines and growth factors in sera. Quantitative RT-PCR of tissues showed expression of inflammatory cytokines and chemokines associated with HIV infection and carcinogenesis. Conclusion: Our findings showed that dysregulation in expression of cytokines and growth factors in patients with multiple infections may contribute to pathogenesis of OSSN and pterygia. The data reinforces the significance of in depth analysis of immune function in HIV-1 OSSN patients with multiple viral infections that has potential for therapy and vaccine development.Publication Viral-Associated Trichodysplasia: Characterization of a Novel Polyomavirus Infection With Therapeutic Insights(2012-02-01) Holler, Phillip D; Dentchev, Tzvete; Simbiri, Kenneth O; Robertson, Erle; Seykora, John J; Wanat, Karolyn A; Rosenbach, MishaBackground Viral-associated trichodysplasia of immunosuppression is a rare cutaneous eruption that is characterized by follicularly based shiny papules and alopecia with characteristic histopathologic findings of abnormally anagen follicules with excessive inner root sheath differentiation. Prior reports have described the histopathologic characteristics on vertical sections; however, to our knowledge, immunohistochemical analysis of polyomavirus proteins has not been previously performed. Observations We discuss the thorough diagnostic evaluation and therapy of an unusual case of viral-associated trichodysplasia due to a newly described human polyomavirus that occurred in a patient with post-treatment chronic lymphocytic leukemia and an abnormal white blood cell count. Unique to our study is the immunohistochemical staining for the polyomavirus middle T antigen, which demonstrated positive staining of cellular inclusions within keratinocytes that compose the inner root sheath. Further evaluation with scanning electron microscopy and polymerase chain reaction analysis of viral DNA confirmed the presence of the virus. Treatment with topical cidofovir resulted in dramatic clinical improvement and hair regrowth. Conclusions Several tools, including immunohistochemical staining for the polyomavirus middle T antigen, can be used to identify the pathogenic virus associated with viral-associated trichodysplasia. This case highlights the utility of multiple diagnostic modalities and a robust response to a topical therapeutic agent, cidofovir.