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Mutations within the env gene of Mason-Pfizer monkey virus: effects on protein transport and SU-TM association
Abstract:
By deletion mutagenesis analyses, we have examined the contribution of the immunosuppressive peptide (ISP) region within the transmembrane (TM) protein of Mason-Pfizer monkey virus to viral maturation and infectivity. Deletion of the entire region (mutant D105) results in the production of an Env precursor that is transport defective and therefore unable to be processed to mature glycoproteins. This mutation results in the release of noninfectious virions devoid of surface glycoproteins. A second deletion that removes the most highly conserved 11 amino acids of the ISP (mutant D33) does not affect the production, transport, or processing of the Env precursor yet produces virions that are noninfectious. The mutation was shown to cause the loss of interaction between the surface (SU) and TM proteins and result in the efficient shedding of gp70 into the culture medium. The released gp70 protein was biologically active and could still bind with high specificity to susceptible target cells. Since the ISP domain may represent an area of contact between SU and TM, it could provide an additional explanation for the amino acid sequence homology observed within this region of a variety of retroviruses.
Insights
Deletion of the immunosuppressive peptide (ISP) region in Mason-Pfizer monkey virus transmembrane (TM) protein impairs viral maturation and infectivity. This region is crucial for surface glycoprotein interaction and viral particle integrity.
Area of Science:
- Virology
- Molecular Biology
- Retroviral Research
Background:
- The transmembrane (TM) protein of Mason-Pfizer monkey virus contains an immunosuppressive peptide (ISP) region.
- Understanding the role of the ISP in viral maturation and infectivity is crucial for retroviral research.
Purpose of the Study:
- To investigate the contribution of the ISP region within the TM protein to viral maturation and infectivity.
- To elucidate the molecular mechanisms by which the ISP affects viral particle formation and infectivity.
Main Methods:
- Deletion mutagenesis was employed to create mutants lacking specific regions of the ISP.
- Analysis of viral particle production, glycoprotein processing, and infectivity was performed.
Main Results:
- Deletion of the entire ISP (mutant D105) resulted in transport-defective Env precursors, noninfectious virions, and absence of surface glycoproteins.
- Deletion of the conserved ISP core (mutant D33) led to noninfectious virions due to loss of surface (SU)-TM protein interaction and gp70 shedding.
- The shed gp70 protein retained biological activity and target cell binding specificity.
Conclusions:
- The ISP region is essential for proper Env precursor processing, TM-SU protein interaction, and viral infectivity.
- The ISP's role in mediating SU-TM interaction may explain conserved amino acid sequences in retroviral TM proteins.