Chioma M. Okeoma, Ph.D.
Ph.D., Massey University, New Zealand, 2006 |
Assistant Professor of Microbiology Campus address: 3-612 BSB Mailing address: 51 Newton Rd. 3-612 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-7906 Email: |
Host-Virus interaction: Host cellular factors involved in virus infection, pathogenesis, and transmission
Mammalian hosts are susceptible to infection by retroviruses including human immunodeficiency virus (HIV) and mouse mammary tumor virus (MMTV) in part, because the latter possess unique strategies designed specifically to evade the host innate and adaptive immune systems. In response, the hosts have developed a number of cellular based defense systems such as apolipoprotein B mRNA-editing enzyme (APOBEC3, A3), and bone marrow stromal cell antigen 2 (BST-2), also known as tetherin or CD317 for virus restriction. Both A3 and BST-2 proteins are expressed in immune cells and both are regulated by cytokines and viruses. Our laboratory is interested in the mechanisms by which A3 and BST-2 proteins inhibit virus infection and the interplay between these restriction factors and the broader innate and adaptive immune systems. We use a combination of ex vivo and in vivo experimental models, biochemical, cellular, genetic, molecular, immunological, and virological assays in our interrogation of virus: host interaction.
In one project, we aim to elucidate the mechanism(s) by which A3 and BST-2 are regulated in vivo and utilize this knowledge to develop more effective therapeutics for viral infections. The expression of A3 and BST-2 are controlled by the host’s cytokine milieu or by invading viruses and/or viral products. Either way, the anti-viral potency of these restriction factors are skewed to either benefit the host or the virus. Currently, we are focused on deciphering the crosstalk between A3 or BST-2 and the broader innate immune system, with a view to defining the signaling events and pathways that regulate the expression and stability of these proteins. In addition, we aim to define the mechanisms by which viruses such as HIV, MLV, and MMTV or their products regulate the expression and stability of A3 and BST-2, to influence their anti-viral potency.
In another project, we are using in vivo experimental model to query the contribution of A3 protein in virus transmission. The loss of A3 protein enhances the rate of milk-borne transmission of MMTV. Indeed, in mice with functional A3, the protein is packaged into MMTV core, resulting in lower rate of virus transmission. We aim to decipher which cell types in milk express A3 and determine the cellular source of A3 packaged into milk-borne viruses. We are also evaluating the impact of A3 in sexual transmission of viruses.
Recent publications
Okeoma CM, Feldman M, Hannenhalli S, and Ross, SR. APOBEC3 proteins made in mammary epithelial cells are packaged into retroviruses and restrict infection by milk-borne virions. Submitted.
Okeoma CM, and Ross SR. Genetics of host resistance to retroviruses and cancer. In "Retroviruses and Insights into Cancer" J.P. Dudley, ed., Springer Science and Business Media, NY, NY. In press.
Okeoma CM, Low A, Bailis W, Fan HY, Peterlin BM, and Ross SR. Induction of APOBEC3 in vivo causes increased restriction of retrovirus infection. J Virol. 2009, 83, 3486-95.
Okeoma CM, Petersen J, and Ross, SR. Expression of murine APOBEC3 alleles in different mouse strains and their effect on mouse mammary tumor virus infection. J Virol. 2009, 83, 3029-38.
Low A, Okeoma CM, Lovsin N, de las Heras M, Thomas H. Taylor TH, Peterlin BM, Ross SR, and Fan H. Enhanced replication and pathogenesis of Moloney murine leukemia virus in mice defective in the murine APOBEC3 gene. Virology 2009, 385, 445-63.
Okeoma CM, Shen M, and Ross SR. A novel block to mouse mammary tumor virus infection of lymphocytes in B10.BR mice. J Virol. 2008, 82, 1314-22.
Okeoma CM, Lovsin N, Peterlin M, Ross S. Murine APOBEC3 is a potent inhibitor of mouse mammary tumor virus. Nature, 2007, 445, 927-30.