viral transcripts are normally excluded from the cy- 
toplasm. Rex functions in a sequence-specific man- 
ner requiring the presence of a Rex response ele- 
ment located in the 3' LTR. This Rex response 
element appears to correspond to a complex RNA 
stem-loop structure (279 nucleotides) that can 
function at any position within the viral RNA but 
, must be present in the sense orientation. Recent 
studies have revealed that the Rex protein is able to 
replace the biological function of the Rev protein in 
the HFV-l system, functioning through a related 
Rev response element. However, this rather re- 
markable genetic complementation is nonrecipro- 
cal, as the HIV-1 Rev protein is unable to function 
via the HTLV-I Rex response element. Mutational 
analysis of the HTLV-I Rex protein has also led to 
the delineation of two peptide domains specifically 
involved in nuclear targeting of this trans-activator 
and its effector function. Mutations in this latter ef- 
fector domain yield trans-dominant repressor pro- 
teins that exert inhibitory effects on the growth of 
both HTLV-I and HIV-1. These trans-dominant Rex 
mutants thus join a small but expanding group of 
dominant negative viral proteins that hold promise 
as a novel approach to antiviral therapy. 
IV Regulation of HIV-1 RepHcation. 
Prior studies have suggested that the 27 kDa Nef 
protein of HIV-1 functions as a negative factor by 
downregulating HIV-1 LTR-mediated transcription. 
To assess the possible role of Nef in the initiation or 
maintenance of latent forms of HIV-1, Dr. Greene 
and his colleagues analyzed the biological effects of 
Nef, using several nef expression vectors for trans- 
fection of multiple cell types. Although these ex- 
pression plasmids directed the synthesis of the 
expected cytoplasmic and myristylated 27 kDa pro- 
tein, Nef exhibited no detectable inhibitory effects 
on the HFV-l LTR in either lymphoid or macro- 
phage cell lines or primary T cells. Furthermore, 
no differences in the replication of nef^ and nef' 
HIV-1 proviruses were discerned. Thus, under the 
conditions of these assays, Nef does not function as 
a negative factor. The true action of this regulato- 
ry viral polypeptide, which appears conserved in 
HIV-1, HIV-2, and simian immunodeficiency virus 
type 1 (SrV-1), remains elusive. 
Dr. Greene is also Professor of Medicine at the 
Duke University Medical Center. 
PUBLICATIONS 
Books and Chapters of Books 
Greene, WC , Bohnlein, E. , Siekevitz, M. , Franza, B.R., Lowenthal, J.W , Wano, Y , and Ballard, D.W 1989. 
Structure and regulation of human receptors for interleukin-2. In The Cellular Basis of Immune Modula- 
tion (Greene, D.R., and Kaplan, J. G., Eds.). New York: Liss, vol 9, pp 269-277. 
Greene, WC , Dukovich, M. , Wano, Y , and Siekevitz, M. 1988. HTLV-I, HIV-1, and human T cell growth. In 
Transposable Elements as Mutagenic Agents. Cold Spring Harbor, NY: Cold Spring Harbor, pp 309-318. 
(Banbury Report 30.) 
Greene, WC, Fung, M., Lowenthal, J.W, Bohnlein, E., and Ballard, D.W 1989. Human receptors for interleu- 
kin-2: structure, function and regulation of gene expression. In Lymphokine Receptor Interactions 
(Fradelizi, D., and Bertoglio, J., Eds.). London: Libbey pp 3-12. 
Lowenthal, J.W , Bohnlein, E. , Ballard, D.W , Siekevitz, M. , Franza, B.R., and Greene, WC. 1988. Regulation of 
IL-2 receptor (Tac) and human immunodeficiency virus gene expression. In Mechanisms of Action and 
Therapeutic Application of Biologicals in Cellular Biology (Groopman, J., Evans, C, and Golde, D., Eds.). 
New York: Liss, vol 100, pp 361-370. 
Articles 
Ballard, D.W , Bohnlein, E. , Lowenthal, J.W , Wano, Y , Franza, B.R., and Greene, WC. 1988. HTLV-I Tax in- 
duces cellular proteins that activate the kB element in the IL-2 receptor a gene. Science 241:1652-1655. 
Bohnlein, E. , Ballard, D.W , Bogerd, H. , Peffer, N.J. , Lowenthal, J.W , and Greene, WC. 1989. Induction of 
interleukin-2 receptor-a gene expression is regulated by post-translational activation of kB specific DNA 
binding proteins. J Biol Chem 264:8475-8478. 
Continued 
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