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Control of Tomato Spotted Wilt Virus Using Transgenic Plants that Produce Virus-Specific Monoclonal Antibodies Progress Report — December 1995

Date 12/26/95

Title of Project Control of tomato spotted wilt virus using

transgenic plants that produce virus-specific monoclonal antibodies

Institution where work is being conducted University of Hawaii

Amount of Endowment Grant $25,000

Covering Period Jan. 95 to Dec. 95

Anticipated Date of Project Completion/Final Report 1996

Individual(s) Conducting Project:

(List Project Leader First)

John S. Hu - Title Assistant Professor

Telephone Number (808) 956-7281

M. Q. Xu - Title Graduate Assistant

Control of Tomato Spotted Wilt Virus Using Transgenic Plants that Produce

Virus-Specific Monoclonal Antibodies

John S. Hu and M. Q. Xu

University of Hawaii

Progress Report to the American Floral Endowment, 12/26/95

A. Project Objectives:

Engineer and express in plants the genes of the monoclonal antibody which

reacts to tomato spotted wilt virus (TSWV).

B. Summary of work

Hybridoma cell lines secreting monoclonal antibodies to TSWV have been

produced. One cell line was selected for the cloning of

the antibody genes. Universal degenerate primers were designed for

PCR amplification of the

variable DNA fragments of heavy and light chains of monoclonal antibodies.

The PCR products were

ligated into one single-chain antibody gene construct and then cloned

into a plasmid vector. The gene

has been subc-loned into a plant transformation vector and transformed

into tobacco Nicotiana

labacian. Preliminary results show that some of the transgenic tobacco

plants were resistant to

systemic infection of TSWV.

C. Results to date

Hybridonia cell lines producing specific monoclonal

antibodies to TSWV have been made. One cell line (TSWV-MAb8C4D6), which

has broad

specificity to TSWV isolates and reacts to the nucleoprotein of TSWV,

has been selected for the

cloning of the antibody genes. Complementary DNAs were produced to

these mRNAs using

oligo-dT as a primer and reverse transcriptase. Universal degenerate

primers were designed for

amplification of variable regions of heavy and light chains of monoclonal

antibodies. Specific cDNA,

which were made to TSWV-MAb mRNA, were used as templates in PCR using

the universal

primers. PCR products were examined in Southern blot hybridization

and were found to be specific

to the TSWV- MAb gene. The PCR products were ligated into one single-chain

antibody gene

construct and then cloned into a plant transformation vector, and used

to transform tobacco.

Hundreds of transgenic plants have been produced. Preliminary results

show that some of the

transgenic tobacco plants developed local lesions on inoculated leaves

without systemic infections on

uninoculated leaves, which suggest the transgenic tobacco plants were

resistant to systemic infection

of TSWV.

D. Future plans covered by the Endowment grant:

The resistant transgenic plants will be

examined in Southern, Northern, and Western blot hybridizations. Gene

segregation of the Fv gene in

the progenies of the transgenic plant lines will be analyzed. The best

lines which show resistance to

TSWV infection will be examined under low and high disease pressures.

E. Anticipated benefits for

floral industry Recent developments in biotechnology have provided

new opportunities to solve

practical agricultural problems. It was recently reported that transgenic

plants expressing a

monoclonal antibody against the coat protein of a tombusvirus have

been produced. Their data show

a delay in symptom development and reduction on virus replication suggesting

a role of the antibodies

in plant protection. The antibody molecules may bind to the nucleoproteins

to prevent uncoating in

the early stage of infection, or bind to the nucleoprotein molecules

to prevent assembly of virions in

the later stages of virus replication. Such a system would be analogous,

in a general way, to the

common antibody defense system in animals. The long term goal of this

research is to control TSWV

using transgenic plants that produce TSWV-specific monoclonal antibodies.

Since TSWV has a very

wide host range, infecting 192 dicotyledonous species in 33 families

and eight monocotyledonous

species in 5 families. If this approach works, the specific genes that

encode monoclonal antibodies to

TSWV could be introduced into many floricultural crops, for control

of this devastating virus disease.

Currently, several other labs are evaluating this antibody-mediated

protection strategy for control of

different plant viruses.