14 
althouqh there are sequences in the viral qenome necessary for integration. 
Dr. Mulligan said subsequent RNA copies made frcm the original proviral copy can 
be packaged and ultimately lead to new proviral insertions in different locations 
in the host cell chronoscme ( s ) . Most retroviruses do not usually kill the 
host cell but establish a more persistent infection and usually insert fran 
one to five provirus copies in various locations in the cell's genane. 
Dr. Joklik asked whether the human genane possesses sequences similar to retroviral 
sequences. Dr. Anderson replied that similar sequences are dispersed throughout 
the human gencrne. It is possible that recombination between retroviral sequences 
and similar sequences in the human genome could occur. 
Dr. Rapp asked how the retrovirus HTLV III/LAV should be treated under the NIH 
Guidelines. He said this virus should probably be classified as a lentivirus. 
Dr. Joklik said the lentiviruses are retroviridieae. These viruses do not 
transform cells but possess reverse transcriptase activity. 
Dr. Anderson asked whether HTLV III/LAV would be considered a class 2 organism. 
He questioned how an am pho trophic vector constructed using HTLV III/IAV genes 
should be handled. He said HTLV III/LAV differs qualitatively from the retroviral 
vectors which are now being constructed for human qene therapy and frcm most 
other retroviruses. HTLV III/LAV is replication competent while human gene 
therapy vectors are replication defective. HTLV III/LAV causes a fatal disease. 
The current amphotropic vectors constructed for human qene therapy applications 
are poorly contagious. Dr. Anderson said some data exist on the effect of an 
amphotropically packaged MoMLV vector carryinq the human ALA (adenosine deaminase) 
qene; there is no evidence of a cytopathic effect on cells in tissue culture. 
Dr. Liberman said cells of the nervous system as well as T4 lymphocytes appear 
to possess receptors recognized by the HTLV III/LAV virus. He said currently 
it is not known if other cells possess these receptors. He added that the 
snail pool of data existinq on HTLV III/LAV suqqests it is not very antigenic. 
The data also suqqest antibodies may not protect against the disease. 
Dr. Gottesman asked why HTLV III/LAV differs fran other retroviruses in its 
toxic effects. 
Dr. Mulligan said FTTLV III/LAV possesses a qene, the "tat" gene, which is 
different fran qenes other retroviruses possess; the "tat" gene appears to be 
a post-transcript ional activator. 
[Rapporteur's Note; The three HTLVs infect T-lymphocytes . Infection by HTLV- I 
or HTLV- 1 1 , the viruses which have been associated with certain types of 
leukemias arri lymphcmas, leads to uncontrolled cell proliferation. HTLV III/LAV 
kills cells it infects. 
All three HTLVs produce trans- act iva t inq proteins that stimulate expression 
of viral qenes. The proteins might also alter cellular gene expression, thus 
disrupting growth control in infected cells. The HTLV III/LAV trans- activating 
qene is in a different location and distinctly different in structure and 
sequence frcm those of HTLV I and HTLV II and has a different activity.] 
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