early as 1963, Howard Temin had shown that replication of retroviruses
was sensitive to not only to the transcription inhibitors Actinomycin
D and alpha-amanitin, but more curiously, nucleoside analogues
like 5-bromodeoxyuridine and cytosine arabinoside, which were
known to inhibit DNA replication. In 1970, the famous "provirus"
hypothesis was made, and shortly afterwards Howard Temin and David
Baltimore separately isolated and described reverse transcriptase
(for which they shared a Nobel Prize).
above scheme for retrovirus replication is fairly well worked
out although details of the second transfer are unclear.
that the 3' U3 becomes the 5'U3 for the next generation of virus.
Similarly, the 5'U5 serves as template for the the 3' U5 for the
integrated form (proviral) of all retroviruses contain transcription
regulatory sequences primarily in Long Terminal Repeats (LTR).
LTR sequences are derived from sequences unique to the 5' end
of viral RNA (U5), from sequences unique to the 3' end of viral
RNA (U3), and from sequences repeated at both ends of the viral
RNA (R). The integrated provirus is larger than the viral genome
but its complexity is the same because of duplication of U3 and
U5 during its synthesis.