TY - JOUR
T1 - Inhibition of retrovirus DNA supercoiling in interferon-treated cells
AU - Huleihel, M.
AU - Aboud, M.
N1 - Funding Information:
We thank the ASCA team for their operation of the satellite, and the ASCA GOF at NASA/GSFC for helpful discussions. We acknowledge the support of the Universities Space Research Association (K. N., I. M. G., T. Y.). K. N. is supported through NASA ADP grant NAG5-7067. This research has made use of data obtained through the HEASARC on-line service, provided by NASA/GSFC.
PY - 1983/1/1
Y1 - 1983/1/1
N2 - The effect of interferon (IFN) on the cytoplasmic synthesis of murine sarcoma virus DNA, its transport to the host nucleus, and its integration into the cellular genome were investigated. For this purpose, at various intervals after infection, DNA was extracted from the cytoplasmic fraction, nuclear Hirt supernatant, and chromosomal DNA pellet. The relative amount of viral DNA was estimated by C0t kinetics analysis of hybridization to murine sarcoma virus-specific [3H]cDNA. IFN was found to delay viral DNA synthesis by about 2.5 h, but the amount of viral DNA eventually formed in IFN-treated cells was comparable to that of the control. The transport of this DNA to the nucleus was delayed by IFN for 6 to 18 h, but once again, all the cytoplasmic viral DNA formed in IFN-treated cells was eventually transferred to their nucleus. However, although the main part of the viral DNA formed in control cells was finally integrated into the host genome, no significant integration was observed in IFN-treated cells. Alkaline sucrose gradient analysis revealed that IFN inhibited the accumulation of supercoiled viral DNA in the nucleus. Since supercoiled viral DNA is considered a precursor to integrated provirus, this observation may suggest that IFN inhibits viral DNA integration by blocking its supercoiling.
AB - The effect of interferon (IFN) on the cytoplasmic synthesis of murine sarcoma virus DNA, its transport to the host nucleus, and its integration into the cellular genome were investigated. For this purpose, at various intervals after infection, DNA was extracted from the cytoplasmic fraction, nuclear Hirt supernatant, and chromosomal DNA pellet. The relative amount of viral DNA was estimated by C0t kinetics analysis of hybridization to murine sarcoma virus-specific [3H]cDNA. IFN was found to delay viral DNA synthesis by about 2.5 h, but the amount of viral DNA eventually formed in IFN-treated cells was comparable to that of the control. The transport of this DNA to the nucleus was delayed by IFN for 6 to 18 h, but once again, all the cytoplasmic viral DNA formed in IFN-treated cells was eventually transferred to their nucleus. However, although the main part of the viral DNA formed in control cells was finally integrated into the host genome, no significant integration was observed in IFN-treated cells. Alkaline sucrose gradient analysis revealed that IFN inhibited the accumulation of supercoiled viral DNA in the nucleus. Since supercoiled viral DNA is considered a precursor to integrated provirus, this observation may suggest that IFN inhibits viral DNA integration by blocking its supercoiling.
UR - http://www.scopus.com/inward/record.url?scp=0020510242&partnerID=8YFLogxK
U2 - 10.1128/jvi.48.1.120-126.1983
DO - 10.1128/jvi.48.1.120-126.1983
M3 - Article
AN - SCOPUS:0020510242
SN - 0022-538X
VL - 48
SP - 120
EP - 126
JO - Journal of Virology
JF - Journal of Virology
IS - 1
ER -