10 
of a viral antigen could chanqe the course of the disease caused by that virus. 
Cross reactivity might also affect the course of a disease; e.g., antibody to 
Herpes simplex I virus affects the response of patients to Herpes simplex II 
virus. 
Dr. Joklik said low levels of antibodies modify patient responses to infection. 
In some cases, low levels of antibody are beneficial; in other cases, they are 
detrimental to the course of the disease. He thought the impact of cross 
reactivity on the course of the disease would also depend on the virus. 
Hr . Simpson suggested data exist in the fermentation industry on worker response 
to protein exposure. Same of this information might be useful in determining 
how individuals respond to protein exposure. 
Dr. Rapp did not think it would be fruitful to review data on immune response 
to proteins since proteins differ in ability to elicit responses. Response to 
exposure to infectious particles differs significantly frcm exposure to proteins; 
infectious particles also differ fran each other in ability to elicit an immine 
response. 
Dr. Gottesman thought the working group should next discuss how retroviruses 
should be treated under the MIH Guidelines. 
Dr. Anderson thouqht the NIH Guidelines as currently written are inadequate in 
dealing with four topics: (1) the retroviral vectors used in human gene therapy; 
(?) the HTLVs; (3) oncogenes in anphotropic vectors; and (4) the consequences 
of nackaqing retroviruses in amphotropic coats. He noted that the NIH Guidelines 
do not address the impact of "packaging lines" since these cell lines did not 
exist when the NIH Guidelines were originally written. Dr. Rapp suggested 
simian retroviruses should also be evaluated. 
Dr. Joklik suggested it might be useful to evaluate these issues in relation to 
procedures investigators are likely to use in the near future; e.g., the vectors 
used in human gene therapy. 
Dr. Gottesman asked the working group to begin with a discussion of the life 
cycle and host range of retroviruses. She asked whether retroviral host range 
related to transformation and tissue specificity. 
[Rapporteur's Note: Adsorption of the retrovirus to the cell is followed by intro- 
duction of the single- stranded RNA qencme into the cytoplasm where it is reverse 
transcribed into a double-stranded DNA molecule containing two long direct 
repeats, termed long terminal repeats (LTRs) , at the ends. Following transport 
to the nucleus, the circularized molecule integrates into the host chromosome 
with the LTRs at the junctions between viral and cellular genanes. The integrated 
provirus serves as the template for synthesis of genomic and subgencmic mRNAs 
encoding the gag , pol , and env functions as well as full-length transcripts of 
the viral genome. The full-length transcripts are packaged into virions vhich 
are shed frcm the cell as infectious virus. 
[449] 
