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Faculty Detail     Name CASEY D MORROW   Campus Address KAUL 802B Zip 0024 Phone 205-934-5705 E-mail caseym@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Secondary  Medicine  Med - Div of Human Gene Therapy Professor Secondary  Microbiology  Microbiology Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Center for AIDS Research  Center for AIDS Research Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor Center  Medicine  Gene Therapy Center Professor

Graduate Biomedical Sciences Affiliations Cellular and Molecular Biology Program  Medical Scientist Training Program  Microbiology

Biographical Sketch  Received his Ph.D. in 1982 from UCLA Department of Microbiology and Immunology in the field of Immunology. Dr. Morrow completed his undergraduate studies in biology and chemistry at the University of California, Irvine (B.A. in Biology, B.S. in Chemistry, 1978). His graduate work in immunology was carried out at UCLA (Ph.D., 1982). His post-doctoral work at UCLA focused on the mechanism of poliovirus replication. His laboratory has focused on HIV for the last 15 years.

Research/Clinical Interest Title Understanding, at the Molecular Level, Virus-host Cell Interactions Description We have focused our studies on a key step in the replication of retroviruses. During replication, retroviruses undergo a process in which the plus strand RNA genome is converted to a DNA intermediate; this process is called reverse transcription and is catalyzed by a viral encoded enzyme, reverse transcriptase. All known retroviruses use a cellular tRNA as a primer for reverse transcriptase. However, different retroviruses use different, but specific, tRNA as their primers for reverse transcription. For example, HIV-1 exclusively uses tRNALys,3 for reverse transcription, while murine leukemia virus (MuLV) and human T-cell leukemia virus (HTLV-1) use tRNAPro. Research in my laboratory is focused on understanding why retroviruses, such as HIV-1, specifically select tRNA for reverse transcription. For these studies, we use contemporary techniques in molecular biology to construct HIV-1, MuLV and HTLV-1 which are forced to use tRNA primers different from the wild type virus. Comparison of the replication in vitro and in vivo using animal model systems of the mutant and wild type viruses provides insights into the importance of the specific tRNA in viral pathogenesis. A second area of interest is to understand how the virus selects the specific tRNA. The normal function of tRNAs in protein synthesis makes the availability of free tRNAs for the virus to use reverse transcription primers scarce within infected cells. How the virus captures specific tRNAs for initiation of reverse transcription necessitates developing a greater understanding of the trafficking of tRNAs in normal and virus infected cells. To study this problem, we have developed a unique complementation system for HIV-1 that allows manipulation of the tRNA primer used for replication. We are using this system to delineate the important elements of the tRNA required for selection and use as a tRNA primer. Finally, we are using the information gained from these studies in the design of new approaches to disrupt the selection process that retroviruses use to capture tRNAs. Ultimately, we will use this information to develop therapeutics designed to disrupt retrovirus (e.g. HIV-1) replication.

Selected Publications  Publication PUBMEDID Yu Q, Morrow CD. Identification of critical elements in the tRNA acceptor stem and T(Psi)C loop necessary for human immunodeficiency virus type 1 infectivity. J Virol. 2001 May;75(10):4902-06.  11312362  Yu Q, Morrow CD. Essential regions of the tRNA primer required for HIV-1 infectivity. Nucleic Acids Res. 2000 Dec 1;28(23):4783-9.  11095691  Kang SM, Zhang Z, Morrow CD. Identification of a human immunodeficiency virus type 1 that stably uses tRNALys,12 rather than tRNALys,3 for initiation of reverse transcription. Virology. 1999 Apr 25;257(1):95-105.  10208924  Kang SM, Morrow CD. Genetic analysis of a unique human immunodeficiency virus type 1 (HIV-1) with a primer binding site complementary to tRNAMet supports a role for U5-PBS stem-loop RNA structures in initiation of HIV-1 reverse transcription. J Virol. 1999 Mar;73(3):1818-27.  9971759  Yu Q, Morrow CD. Complementarity between 3' terminal nucleotides of tRNA and primer binding site is a major determinant for selection of the tRNA primer used for initiation of HIV-1 reverse transcription. Virology. 1999 Feb 1;254(1):160-8.  9927583  Zhang Z, Kang SM, Morrow CD. Genetic evidence of the interaction between tRNA(Lys,3) and U5 facilitating efficient initiation of reverse transcription by human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1998 Jul 20;14(11):979-88.  9686644  Zhang Z, Kang SM, Li Y Morrow CD. Genetic analysis of the U5-PBS of a novel HIV-1 reveals multiple interactions between tRNA and RNA genome required for initiation of reverse transcription. RNA. 1998 Apr;4(4):394-406.  9630246  Zhang Z, Yu Q, Kang SM, Buescher J, Morrow CD. Preferential completion of human immunodeficiency virus type 1 proviruses initiated with tRNA3Lys rather than tRNA1,2Lys. J Virol. 1998 Jul;72(7):5464-71.  9621002  Li Y, Zhang Z, Kang SM, Buescher JL, Morrow CD. Insights into the interaction between tRNA and primer binding site from characterization of a unique HIV-1 virus which stably maintains dual PBS complementary to tRNA(Gly) and tRNA(His). Virology. 1997 Nov 24;238(2):273-82.  9400600  Li Y, Zhang Z, Wakefield JK, Kang SM, Morrow CD. Nucleotide substitutions within U5 are critical for efficient reverse transcription of human immunodeficiency virus type 1 with a primer binding site complementary to tRNA(His). J Virol. 1997 Sep; 71(9):6315-22.  9261348

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