title: Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.
abstract: Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Meghna
authors.initials: M
authors.lastname: Verma
authors.affiliation: Department of Mathematics, Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Samantha
authors.initials: S
authors.lastname: Erwin
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Vida
authors.initials: V
authors.lastname: Abedi
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoops
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leber
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.affiliation: Department of Mathematics, Virginia Tech, Blacksburg, VA, United States of America.
authors.forename: Stanca M
authors.initials: SM
authors.lastname: Ciupe
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D008954:Models, Biological; D009061:Mouth Mucosa / Q000821:virology*; D009857:Oncogenes; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D011379:Prognosis; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D054322:tat Gene Products, Human Immunodeficiency Virus