chowdhury

Faculty

Shafiqul I. Chowdhury
Professor of Molecular Virology

Laboratory:

Phone: 225-578-9681
Fax: 225-578-9701

Education:
DVM Bangladesh Agricultural University, Bangladesh • M.S. Bangladesh Agricultural University, Bangladesh • Goethe Institute, Mannheim, Germany, German • Ph.D. Free University of Berlin, Germany, Virology

Research Interests:

My research is in the area of molecular virology, neurovirology, neuro-pathogenesis and recombinant herpesvirus vaccine technology.

Role of envelope proteins/glycoproteins in Bovine herpesvirus types 1 and 5 (BHV-1 and BHV-5) differential neuropathogenesis.
BHV-1 and BHV-5 are significant viral pathogens of cattle. BHV-1 (also known as infectious rhinotracheitis virus or IBR) causes upper respiratory disease and abortions in cattle, while BHV-5 (also known as encephalitic bovine herpesvirus) causes neurological disease in calves. Despite the widespread use of vaccines to control BHV-1, this virus continues to be a major cause of yearly economic loss to the cattle industry. Genetically these two viruses are closely related (85% DNA homology) yet cause distinct diseases in cattle. A detailed understanding of the molecular mechanisms of these diseases is important in designing prophylactic vaccines. A molecular genetic approach is being used to define the molecular basis of BHV-1 and BHV-5 differential neuropathogenesis in calves. We have developed a rabbit model that distinguishes BHV-1 and BHV-5 based on their differential neuropathogenesis (S.I. Chowdhury et al., J. Comp. Pathol. 117:295-310, 1997). Using this rabbit model, we have determined that BHV-5 gE and Us9 envelope proteins are essential for BHV-5 neurovirulence in rabbits. While the loss of neurovirulence in the Us9-deleted BHV-5 could be rescued by BHV-1 Us9, the loss of neurovirulence in the gE-deleted BHV-5 could not be complemented by BHV-1 gE. Relative to a gE cytoplasmic tail-truncated BHV-5 which retained significant neurovirulence, deletion of a glycine-rich region within the gE ecto domain resulted in significant reduction in neuropathogenicity of the virus. In the future, we plan to determine whether the glycine-rich gE sequences specifically interact/bind to a neuronal protein(s).

Directional spread of bovine herpesvirus type 1 (BHV-1) within the nervous system.
During primary infection, BHV-1 replicates in the nasal and ocular epithelium and then invades the sensory nerve endings of the trigeminal nerve in the nasopharynx and eye. Subsequently, the capsids are transported by retrograde axonal transport to the neuronal cell bodies in the trigeminal ganglia (TG) where they establish life-long latency. Animals latently infected with BHV-1 are potential sources of BHV-1 infection since the reactivated virus in the TG can be transported back to nose/eye anterogradely and is shed in the nasal and ocular secretions. We have determined that the gE-, entire gE cytoplasmic tail-, Us9- and Us9 acidic-domain-deleted viruses have defective anterograde transport. Our future goals are: i) To narrow down the region within the gE cytoplasmic tail further that is important for anteorograde axonal transport and ii) To identify neuronal proteins that interact with the Us9 acidic domain and/or gE cytoplasmic tail sequences and promote anterograde axonal transport.

Regulation of pathogenicity and immunogenicity by BHV-1 envelope glycoproteins gM/gN.
BHV-1, like other alpha herpesviruses can evade the immune recognition at early times post-infection. Recently, it was discovered that envelope glycoprotein gN, which forms complex with glycoprotein M, interferes with the cellular immune response by interfering with transporter associated with antigen presentation (TAP) function. The goals of this project are to identify the gN domain(s) necessary for TAP and gM binding and construct BHV-1 mutants that do not express gM or gN or lack the gN TAP binding domain, and study these mutants with respect to inhibiting TAP and inducing disease in cattle.

HSV-1 neuropathogenesis studies
In collaboration with Dr. Kousoulas’ lab, my laboratory has initiated projects to study HSV-1 neuropathogenesis in our rabbit model. We plan to generate HSV-1 glycoprotein E (gE), gM, Us9 and gK mutants and characterize their neuronal transport in vitro in primary neuronal cultures and neuropathogenicity in rabbits.

Current Research Support:
1. USDA/NRI animal protection program: Functional analysis of BHV-1 gE and Us9 sub-domains required for anterograde neuronal spread. (12/08 to 11/11).
2. USDA/NRI-animal protection: Regulation of pathogenicity and immunogenicity by BHV-1 envelope glycoproteins gM/gN (10/07 to 09/10).

Selected Publications

Saira, K., S. Chowdhury, N. Gandreault, L. da Silva, G. Henderson, A. Doster and C. Jones (2008). The Zinc RING finger of bovine herpesvirus 1-encoded bICP0 protein is crucial for viral replication and virulence. J. Virol. 82, no.24 (In Press).

Brum M, Coats C., Sangena B.R, Doster.A., Jones, C. and Chowdhury.S.I. Role of Envelope proteins gE in the anterograde transport of BHV-1 following reactivation in the Trigeminal Ganglia. J. Neuro Virology (In Press.).

Koppers-Lalic D, Verweij MC, Lipińska AD, Wang Y, Quinten E, Reits EA, Koch J, Loch S, Rezende MM, Daus F, Bieńkowska-Szewczyk K, Osterrieder N, Mettenleiter TC, Heemskerk MH, Tampé R, Neefjes JJ, Chowdhury SI, ing ME, Rijsewijk FA, Wiertz EJ (2008). Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP. Plos Pathogen. 30;4(5):e1000080

Liu, Z-F., M. Brum, A. Doster, C. Jones and S.I. Chowdhury (2008). A bovine herpesvirus type 1 mutant virus specifying a carboxyl-terminal truncation of glycoprotein E is defective in anterograde neuronal transport in rabbits and calves. J. Virol. 82: 7432-7442.

Jones, C. and S. Chowdhury (2007). A review of the biology of bovine herpes-virus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex, and development of improved vaccines. Anim. Health Res. Rev. 8:187-205.

Butchi, N.B, Jones, C., Perez.S, Doster.A, and Chowdhury.S.I (2007). Role of Envelope protein Us9 in the anterograde transport of BHV-1 following reactivation in the Trigeminal Ganglia. J. Neurovirology. 13:384-388.

Al-Mubarak-A., J. Simon, M.D. Burton and S.I. Chowdhury (2007). Glycoprotein E(gE) specified by Bovine herpesvirus type5 (BHV-5) enables trans-neuronal virus spread and neurovirulence without being a structural component of enveloped virions. Virology. 365:398-409

Chowdhury, S.I., S. Mahmood, J. Simon, A. Al-Mubarak and Y. Zhou (2006). The Us9 gene encoded by bovine herpesvirus type 1 (BHV-1) effectively complements a Us9-null bovine herpesvirus 5 (BHV-5) for anterograde transport, neurovirulence and neuroinvasiveness in a rabbit model. J. Virol. 80: 4396-4405.

Al-Mubarak, A. and Chowdhury, S.I. (2004). In the absence of glycoprotein I (gI), gE determines bovine herpesvirus type 5 neuroinvasiveness and neurovirulence. J. Neurovirology. 10: 233-243.

Al-Mubarak, A, Zhou, Y., and Chowdhury, S.I . (2004). A glycine rich region in the ecto domain of BHV-5 gE is important for BHV-5 neuropathogenesis. J. Virol. 78, 4806-4816.

Chowdhury, S.I., Onderci, M., Bhattacharjee, P.S., Al-Mubarak, A., Weiss, M.L., and Zhou, Y.J. (2002). Bovine herpesvirus type 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. J. Virol.76, 3839-3851.

Huang, J., Chowdhury, S.I., and Weiss, M.L. (2002). Distribution of sympathetic preganglionic neurons innervating the kidney in the rat: PRV transneuronal tracing and serial reconstruction. Autonomic Neuroscience 95: 57-70.

Weiss, M.L., Chowdhury, S.I., Patel, K.P., Kenney, M.J., and Huang, J. (2001). Neural circuitry of the kidney: NO containing neurons. Brain Research 919: 269-282

Weiss, M.L., Dobbs, M.E., Mohankumar, P.S., Chowdhury,S.I., Sawrey,R., Gueva-Guzman,R., and Huang, J. (2001). The estrous cycle affects pseudorabies virus (PRV) infection of the CNS. Brain Research 893: 215-226.

Chowdhury SI, Lee, BJ, Onderci1, M., Weiss, ML, and Mosier, D. 2000. Neurovirulence of glycoprotein C(gC)-deleted bovine herpesvirus type-5 (BHV-5) and BHV-5 expressing BHV-1 gC in a rabbit seizure model. J. Neurovirology. 6(4): 284 - 295.

Chowdhury SI, Lee, BJ., Ozkul, A., and M. L. Weiss. (2000). Bovine Herpesvirus type-5 (BHV-5) Glycoprotein E (gE) is Important for Neuroinvasiveness and Neurovirulence in the Olfactory Pathway of the Rabbit. J. Virol.74, 2094-2106.