12 
sarcana virus proteins in mammalian cells. In sane viruses there are tissue- 
specific controls on transcriptional activity.] 
Dr. Mulligan said the most important factors in determining host range are 
receptor site recognition, attachment, and penetration. The viral coat protein 
plays the major role in receptor recognition and on host range. He said sane 
post-penetration restriction of replication occurs in seme cell types. 
Hcwever, post-penetration restriction does not have a major impact on host 
range. In addition, if transcriptional specificity is changed, the tropism of 
the virus may change; for example, a retrovirus will preferentially replicate 
in T cells if the retrovirus has that transcriptional specificity. 
Dr. Mulligan said a range of manipulations, such as modification of virally 
encoded envelope proteins, can affect host range. Dr. Mulligan said this 
"pseudotyping" or "phenotypic mixing" affects the host range for one generation 
unless the modified protein is an envelope protein encoded by the virus. 
[Rapporteur's Note; Encapsidated RNA is budded from the plasma membrance at 
locations where the membrane is modified by insertion of viral proteins and 
an exclusion of host cell proteins. Virion maturation involving proteolytic 
cleavage of certain proteins and changes in morphology of the internal virion 
core follows budding. 
The process of budding is not virus species-specific; the envelope glycoproteins 
need not be from the retrovirus family. In addition, encapsidation or packaging 
is not completely species specific although it is more specific than budding. 
Thus, proteins in a retroviral virion can be encoded by the genane in the 
virion (replication-competent retrovirus), by a complementing viral genane 
(helper replication-competent retrovirus or superinfecting retrovirus), or 
by a helper cell (cell with viral genomes deleted of encapsidation seguences 
and constitutively expressing virion proteins.) 
The envelope-specific control of host range can be abrogated for one virus 
cycle by fusion of virions to resistant cells using inactivated Sendai virus 
or polyethylene glycol. 
A virus composed of a genome from one retrovirus and envelope proteins from 
another virus is termed a "pseudotype." A pseudotype represents pseudo- 
phenotypic mixing; upon infection the genome of the pseudotype will only express 
genome proteins and progeny particles will be encapsidated by these genomic 
proteins. ] 
Dr. Anderson said ecotropic viruses (viruses isolated from mouse cells and 
only infecting cells of the same species) do not present a hazard to humans 
since their host range is limited. Viruses with amphotropic coats should on 
the other hand be evaluated; the NIH Guidelines might address this situation. 
Dr. Landy asked what determines which proteins the virus incorporates in its 
coat. 
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