The focus of my research is to understand the molecular mechanisms of the interaction between Cytomegalovirus (HCMV) and host cells. In particular the topics I'm interested in are:
- Identify the mechanisms of chronic disease due to HCMV persistent infection: the importance and the interest of HCMV as a pathogen has increased over the past two decades, with the escalation in the number of immunosuppressed patients, either undergoing immunosuppressive therapy following solid organ or bone marrow transplantation. Epidemiological and animal studies have been linked HCMV infection to the development of vascular diseases such as atherosclerosis, restenosis and transplant vascular sclerosis, however the mechanisms involved in this process remain unknown. A growing body of evidence supports a role for angiogenesis and wound healing in the development of vascular disease, for this reason the goal of my laboratory is to understand how the virus induces angiogenesis. In particular we are trying to identify the class of viral gene(s) involved in this process as well as the critical cellular factors secreted from infected cells induced by these gene(s) that induce angiogenesis.
- Establish human cytomegalovirus (HCMV) as a new human vaccine vector platform. Unique characteristics of CMV are: a) ability to re-infect and disseminate through the population regardless of prior CMV immunity b) a capacity to induce high levels of humoral and cellular immune responses against the heterologous pathogen target antigen c) a capacity to maintain these responses essentially for the life of the host d) induction of 'effector memory'-based immunity (T cells localized to mucosal effector sites with immediate effector function) and e) the potential to insert large cassettes in which theoretically over 50kb of the viral genome can be replaced with foreign DNA. A vaccine strategy using a CMV-based vector expressing antigens from different pathogens may be ideally suited for several reasons: it can help us to study the role of the T-cell response in the control of the disease and can re-infect and establish a persistent infection regardless the host CMV immunity.
Dr. Patrizia Caposio received her B.Sc in Biology from University of Turin, Italy in 1999. She obtained her Master in Microbiology and Virology in 2004 and the doctorate degree in Biochemistry in 2007 at the Department of Public Health and Microbiology, University of Turin. In the period 2005-2009 she became research assistant professor at the University of Turin. She is currently an assistant scientist at the Vaccine and Gene Therapy Institute, OHSU.
Kim JH, Collins-McMillen D, Caposio P, Yurochko AD. Viralbinding-induced signaling drives a unique and extended intracellulartrafficking pattern during infection of primary monocytes. Proc Natl Acad Sci US A. 2016 Aug 2;113(31):8819-24. doi: 10.1073/pnas.1604317113.
Caviness K, Bughio F, Crawford LB, Streblow DN, Nelson JA,Caposio P, Goodrum F.Complex Interplay of the UL136 Isoforms BalancesCytomegalovirus Replication and Latency. MBio. 2016 Mar 1;7(2):e01986. doi:10.1128/mBio.01986-15.[PMID: 26933055]
Crawford LB, Streblow DN, Hakki M, Nelson JA, Caposio P.Humanizedmouse models of human cytomegalovirus infection. Curr Opin Virol. 2015Aug;13:86-92. doi: 10.1016/j.coviro.2015.06.006. [PMID: 26118890]
Tsuda Y, Parkins CJ, Caposio P, Feldmann F, Botto S, Ball S,Messaoudi I, Cicin-Sain L, Feldmann H, Jarvis MA. A cytomegalovirus-basedvaccine provides long-lasting protection against lethal Ebola virus challengeafter a single dose. Vaccine. 2015 May 5;33(19):2261-6. doi:10.1016/j.vaccine.2015.03.029. [PMID: 2582006]
- MacManiman JD, Meuser A, Botto S, Smith PP, Liu F, Jarvis MA, Nelson JA, Caposio Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis. P. MBio. 2014 Oct 28;5(6):e02035. (doi: 10.1128/mBio.02035-14.) [PMID: 25352622, PMCID: PMC4217178]
- Klyushnenkova, E.N., Kouiavskaia, D.V, Parkins, C.J, Caposio, P, Botto, S, Alexander, R.B, Jarvis, M.A. A cytomegalovirus-based vaccine expressing a single tumor-specific CD8 + T-cell epitope delays tumor growth in a murine model of prostate cancer. J Immunother. 2012 Jun;35(5):390-9. (doi: 10.1097/CJI.0b013e3182585d50.) [PMID: 22576344, PMCID: PMC3366429]
- Tierney R, Nakai T, Parkins CJ, Caposio P, Fairweather NF, Sesardic D, Jarvis MA. A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C induces sustained levels of protective tetanus toxin antibodies in mice. Vaccine. 2012 Apr 26;30(20):3047-52. (doi: 10.1016/j.vaccine.2012.02.043.) [PMID: 22241980, PMCID: PMC3248471] Epub 2011 Dec 29.
- Umashankar M, Petrucelli A, Cicchini L, Caposio P, Kreklywich CN, Rak M, Bughio F, Goldman DC, Hamlin KL, Nelson JA, Fleming WH, Streblow DN, Goodrum F. A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog. 2011 Dec;7(12):e1002444. (doi: 10.1371/journal.ppat.1002444.) [PMID: 22241980, PMCID: PMC3248471] Epub 2011 Dec 29.
- Tsuda Y, Caposio P, Parkins CJ, Botto S, Messaoudi I, Cicin-Sain L, Feldmann H, Jarvis MA. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. PLoS Negl Trop Dis. 2011 Aug;5(8):e1275. (doi: 10.1371/journal.pntd.0001275.) [PMID: 21858240, PMCID: PMC3153429] Epub 2011 Aug 9.
- Botto S, Streblow DN, DeFilippis V, White L, Kreklywich CN, Smith PP, Caposio P. IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. Blood. 2011 Jan 6;117(1):352-61. (doi: 10.1182/blood-2010-06-291245.) [PMID: 20930069, PMCID: PMC3037756] Epub 2010 Oct 7.