Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
SIV host range specificity transfer to recombinant HIV-1 virions via SIV envelope glycoproteins.
Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 11. Unique Identifier : AIDSLINE PRIM10/93200958 Johnston PB; Hunter E; Department of Microbiology, University of Alabama, Birmingham; 35294.
Abstract:
The host range specificity of simian immunodeficiency virus, SIVmac239, appears to be modulated by the cytoplasmic domain of its envelope glycoprotein. Propagation of SIVmac239 in HUT78 cells results in truncation of the transmembrane (TM) protein to 207-211 amino acids. We sought to determine whether further truncations might be tolerated for infectivity, and whether these truncations might change the host range of the virus. We have created a series of C-terminal truncation mutants which result in TM proteins of 163-207 amino acids, relative to a wild-type 354 amino acid protein. The truncated env genes, expressed from an SV-40 vector, were transported and processed normally, with one notable exception. We next examined syncytium formation by these recombinant glycoproteins. Interestingly, truncations of the TM protein to 193 and 191 amino acids, as well as tm207, induced syncytium formation in a manner comparable to wild-type in a variety of T-cell lines, including CEMX174, C8166 and HUT78. To examine the effect of these truncations on infectivity and host range specificity, proviral constructs were created. The wild-type and mutant viruses with TM proteins of 191-207 aa efficiently infected CEMX174 cells, whereas only virus containing the 207 aa TM protein efficiently infected HUT78 cells. Delayed kinetics of infection were noted for virions containing tm193 and tm354. Thus, the spontaneously occurring tm207 truncation in virus confers a novel growth advantage in this cell line. It is interesting that expression of the wild-type glycoprotein alone allows unrestricted fusion with HUT78 cells, suggesting that the inhibitory effect in infectivity is virus specific. To further examine how the host range of the virus is modulated by the cytoplasmic domain truncations, we have complemented an env-defective HIV-1 virus with these SIV envelope glycoproteins. Numerous HIV-1 and SIV envelope glycoprotein mutants were assayed within this complementation system, to correlate the complementation data with viral infectivity. With SIV, both the wild-type and tm207 SIV envelope glycoproteins were able to efficiently mediate HIV-1 entry into CEMX174 and C8166 cell lines. In contrast, HIV virions carrying the wild-type SIV glycoprotein could not infect HUT78 and H9 cells; whereas, the virions containing the 207 amino acid SIV TM protein were as infectious as in CEMX174 cells. These complementation studies combined with virus infectivity data suggest that the defect in infectivity of SIVmac239 (tm354) occurs at an early attachment/entry stage of the life cycle.
Keywords: Animal Cell Line Genetic Complementation Test Human HIV-1/*GENETICS Recombination, Genetic SIV/*GENETICS/*PHYSIOLOGY T-Lymphocytes Viral Envelope Proteins/*GENETICS Virion/*GENETICS Virus Replication ABSTRACT 930630
M9361062
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
