scripts corresponding to the stem-loop in TAR are 
recovered. Quantitative differences in nuclear run- 
ons and recoveries of RNA can be interpreted as 
representing premature termination of transcrip- 
tion. Alternatively, TAT could prevent rapid degra- 
dation of nascent RNA in the nucleus. Research ef- 
forts have focused on exact requirements of 
' cis-acting sequences in TAR and possible interac- 
tions between TAT and TAR. First, Dr. Peterlin de- 
termined that the stem-loop in TAR is required for 
trans-activation by TAT and has to be located very 
close to the site of initiation of transcription. Sec- 
ond, proteins that bind to TAR DNA are not re- 
quired for trans-activation. Third, not only the 
structure of TAR RNA but also sequences near the 
loop of the stem-loop in TAR are very important. So 
far, no specific binding of TAT to TAR RNA has been 
observed. Moreover, trans-activation by TAT could 
not be reproduced in simple in vivo or in vitro sys- 
tems, including Escherichia coli, yeast, Xenopus 
oocytes, and HeLa nuclear extracts. 
B. Activation of HIV gene expression. In contrast to 
effects of TAT that occur after transcription has 
initiated, there are inducible trans-acting factors 
that are required for initiation of HIV transcription. 
These include NF-kB and NFAT-1 (nuclear factor of 
activated T cells), which bind to the transcriptional 
enhancer and upstream U3 sequences, respectively. 
Subtle differences between two isolated HIV 
viruses, HIV-1 and HIV-2, were noted in mecha- 
PUBLICATIONS 
nisms of transcriptional activation. These include 
lower levels of activation of HIV-2 as compared 
with HIV-1 and the lack of a second NF-kB site in 
HIV-2, which might explain longer latency and at- 
tenuated clinical course observed with HIV-2. Co- 
operative and multiplicative interactions between 
activation of transcription and trans-activation by 
TAT were observed, implying once again that these 
mechanisms are distinct and separable. 
In addition to studies on the activation of the 
HIV long terminal repeats (LTRs) by mitogens and 
T cell agonists. Dr. Peterlin investigated possible 
roles of other infections in the pathogenesis of 
AIDS. In collaboration with Ben Yen (University of 
California at San Francisco), he found that the X 
protein of hepatitis B, which is a known transcrip- 
tional activator, increases expression from the 
HIV-1 LTR in T cells. This activation occurs at the 
NF-kB sites and is independent of T cell activation. 
Thus hepatitis B virus could be an important cofac- 
tor in HIV disease progression. Additionally, in 
studies with Dr. Paul Luciw (University of California 
at Davis), Dr. Peterlin found that immediate early 
trans-activators of cytomegalovirus (CMV) also in- 
crease HIV-l-directed gene expression. In contrast 
to X protein, CMV trans-activators act on the HIV-1 
TATA box. 
Dr. Peterlin is also Associate Professor of Medi- 
cine and of Microbiology and Immunology at the 
University of California at San Francisco. 
Books and Chapters of Books 
Peterlin, B.M. 1988. Transcriptional regulation of HIV In Retroviruses of Human A.I.D.S. and Related Animal 
Diseases (Girard, M., and Valette, L., Eds.). Lyon: Fondation Marcel Merieux, pp 95-99. 
Peterlin, B.M. 1989. The mechanism of HIV rrans-activation by the tat gene product. In DNA-Protein Interac- 
tions in Transcription (Gralla, J.D., Ed.). New York: Liss, vol 95, pp 221-228. (UCLA Symposia on Molecu- 
lar and Cellular Biology.) 
Articles 
Caiman, A.F., and Peterlin, B.M. 1988. Evidence for a trans-acting factor that regulates the transcription of 
class II major histocompatibility complex genes; genetic and functional analysis. Proc Natl Acad Sci USA 
85:8830-8834. 
Fronek, Z., Timmerman, L.A., Alper, C.A., Hahn, B.H., Kalunian, K., Peterlin, B.M. , and McDevitt, H.O. 1988. 
Major histocompatibility complex associations with systemic lupus erythematosus. yl77z/Afe^/85(S6A):S42- 
S44. 
Peterlin, B.M., and Luciw, PA. 1988. Molecular biology oiHYW.AIDS 2(Suppl 1):S29-S40. 
Continued 
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