Gregory Alan Sowd, Ph.D.

Research Instructor
Faculty Appointments
Research Instructor in Pathology, Microbiology and Immunology
Ph.D., Biological Science, Vanderbilt University, Nashville, TennesseeB.S., Biochemistry, Virginia Polytechnic Institute, Blacksburg, Virginia
Research Description
HIV-1 is the causative agent of the worldwide AIDS epidemic, affecting greater than 30 million people worldwide. Although the underlying HIV-1 infection can be effectively suppressed with current anti-retroviral regimens, no magic bullet exists to cure infected individuals with the mutability of HIV remaining a constant problem. To this end, I study host factors that interact with the HIV-1 capsid protein CA.

The HIV-1 capsid composed of the single viral protein CA is more than a shell that protects the viral genomic payload from immune sensing and the environment. CA functions to escort the viral genome to the nucleus thereafter facilitating nuclear entry (Yamashita et al. Journal of Virology. 2004.) and viral integration site preferences (Sowd et al. PNAS. 2016.). Further, CA mutations that alter capsid stability have severe consequences for HIV-1 infection (Forshey et al. Journal of Virology. 2002.), and CA is the most genetically fragile region of the viral genome (Rihn et al. PLoS Pathogens. 2013.) underscoring the importance of the protein to productive infection. Thus, CA is a prime target for HIV-1 anti-retrovirals (Shi et al. Journal of Virology 2011.). With this in mind, we study host proteins and metabolites that modulate HIV-1 CA function during viral entry, integration, and maturation using diverse techniques including deep sequencing, biochemical characterization of HIV-1 virions/capsids, and gene knockout studies of host factors.
Research Keywords
Genomics, molecular biology, genetics and biochemistry of HIV-1 infection, HIV-1 capsid function, retrovirus integration targeting
Anderson-Daniels J, Singh PK, Sowd GA, Li W, Engelman AN, Aiken C. Dominant Negative MA-CA Fusion Protein Is Incorporated into HIV-1 Cores and Inhibits Nuclear Entry of Viral Preintegration Complexes. J. Virol [electronic-print]. 2019 Nov 11/1/2019; 93(21): PMID: 31413124, PMCID: PMC6803256, PII: JVI.01118-19, DOI: 10.1128/JVI.01118-19, ISSN: 1098-5514.

Achuthan V, Perreira JM, Sowd GA, Puray-Chavez M, McDougall WM, Paulucci-Holthauzen A, Wu X, Fadel HJ, Poeschla EM, Multani AS, Hughes SH, Sarafianos SG, Brass AL, Engelman AN. Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration. Cell Host Microbe [print-electronic]. 2018 Sep 9/12/2018; 24(3): 392-404.e8. PMID: 30173955, PMCID: PMC6368089, PII: S1931-3128(18)30430-X, DOI: 10.1016/j.chom.2018.08.002, ISSN: 1934-6069.

Zhu Y, Wang X, Forouzmand E, Jeong J, Qiao F, Sowd GA, Engelman AN, Xie X, Hertel KJ, Shi Y. Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation. Mol. Cell [print-electronic]. 2018 Jan 1/4/2018; 69(1): 62-74.e4. PMID: 29276085, PMCID: PMC5756121, PII: S1097-2765(17)30890-0, DOI: 10.1016/j.molcel.2017.11.031, ISSN: 1097-4164.

Saito A, Ferhadian D, Sowd GA, Serrao E, Shi J, Halambage UD, Teng S, Soto J, Siddiqui MA, Engelman AN, Aiken C, Yamashita M. Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74. J. Virol [electronic-print]. 2016 Jun 6/15/2016; 90(12): 5808-23. PMID: 27076642, PMCID: PMC4886767, PII: JVI.03116-15, DOI: 10.1128/JVI.03116-15, ISSN: 1098-5514.

Rasheedi S, Shun MC, Serrao E, Sowd GA, Qian J, Hao C, Dasgupta T, Engelman AN, Skowronski J. The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV-1 Integration into Genes. J. Biol. Chem [print-electronic]. 2016 May 5/27/2016; 291(22): 11809-19. PMID: 26994143, PMCID: PMC4882448, PII: M116.721647, DOI: 10.1074/jbc.M116.721647, ISSN: 1083-351X.

Sowd GA, Serrao E, Wang H, Wang W, Fadel HJ, Poeschla EM, Engelman AN. A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2016 Feb 2/23/2016; 113(8): E1054-63. PMID: 26858452, PMCID: PMC4776470, PII: 1524213113, DOI: 10.1073/pnas.1524213113, ISSN: 1091-6490.

Sowd GA, Mody D, Eggold J, Cortez D, Friedman KL, Fanning E. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products. PLoS Pathog. 2014 Dec; 10(12): e1004536. PMID: 25474690, PMCID: PMC4256475, PII: PPATHOGENS-D-14-01844, DOI: 10.1371/journal.ppat.1004536, ISSN: 1553-7374.

Sowd GA, Li NY, Fanning E. ATM and ATR activities maintain replication fork integrity during SV40 chromatin replication. PLoS Pathog [print-electronic]. 2013; 9(4): e1003283. PMID: 23592994, PMCID: PMC3617017, PII: PPATHOGENS-D-12-02923, DOI: 10.1371/journal.ppat.1003283, ISSN: 1553-7374.

Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, Vila S, Gai D, Fanning E, Chen XS. Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase a-primase. J. Biol. Chem [print-electronic]. 2012 Aug 8/3/2012; 287(32): 26854-66. PMID: 22700977, PMCID: PMC3411022, PII: M112.363655, DOI: 10.1074/jbc.M112.363655, ISSN: 1083-351X.

Sowd GA, Fanning E. A wolf in sheep's clothing: SV40 co-opts host genome maintenance proteins to replicate viral DNA. PLoS Pathog [print-electronic]. 2012; 8(11): e1002994. PMID: 23144614, PMCID: PMC3493471, PII: PPATHOGENS-D-12-01811, DOI: 10.1371/journal.ppat.1002994, ISSN: 1553-7374.

Sowd G, Wang H, Pretto D, Chazin WJ, Opresko PL. Replication protein A stimulates the Werner syndrome protein branch migration activity. J. Biol. Chem [print-electronic]. 2009 Dec 12/11/2009; 284(50): 34682-91. PMID: 19812417, PMCID: PMC2787331, PII: M109.049031, DOI: 10.1074/jbc.M109.049031, ISSN: 1083-351X.

Opresko PL, Sowd G, Wang H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS ONE [print-electronic]. 2009; 4(3): e4825. PMID: 19283071, PMCID: PMC2653227, DOI: 10.1371/journal.pone.0004825, ISSN: 1932-6203.

Sowd G, Lei M, Opresko PL. Mechanism and substrate specificity of telomeric protein POT1 stimulation of the Werner syndrome helicase. Nucleic Acids Res [print-electronic]. 2008 Aug; 36(13): 4242-56. PMID: 18583366, PMCID: PMC2490755, PII: gkn385, DOI: 10.1093/nar/gkn385, ISSN: 1362-4962.