Across the Hall from Pioneers.

Alan Rein

doi:10.3390/v13030491

Abstract

I was fortunate to be associated with the lab of Stephen Oroszlan at the US National Cancer Institute from ~1982 until his conversion to Emeritus status in 1995. His lab made groundbreaking discoveries on retroviral proteins during that time, including many features that could not have been inferred or anticipated from straightforward sequence information. Building on the Oroszlan lab results, my colleagues and I demonstrated that the zinc fingers in nucleocapsid proteins play a crucial role in genomic RNA encapsidation; that the N-terminal myristylation of the Gag proteins of many retroviruses is important for their association with the plasma membrane before particle assembly is completed; and that gammaretroviruses initially synthesize their Env protein as an inactive precursor and then truncate the cytoplasmic tail of the transmembrane protein, activating Env fusogenicity, during virus maturation. We also elucidated several aspects of the mechanism of translational suppression in pol gene expression in gammaretroviruses; amazingly, this is a fundamentally different mechanism of suppression from that in most other retroviral genera.

Highlights

I was fortunate to be associated with the lab of Stephen Oroszlan at the US National Cancer
Simple cell-fractionation experiments showed that the mutant Gag protein was soluble in cell lysates, whereas in the controls, wild-type Gag protein was largely bound to membranes or other large, pelletable structures in the cell. These results confirmed that the N-terminal glycine was necessary for myristylation, and demonstrated that the myristyl modification was crucial for membrane association and virus production by the Murine Leukemia Virus (MLV) Gag protein
Alan Schultz and I followed up these original observations with a further analysis of the behavior of the unmyristylated mutant Gag protein. We found that it was metabolically stable within cells and did not undergo the maturation cleavages that occur after the release of wild-type virus [22]. We reported that it did not participate in intracellular particle assembly, even in the presence of a normally assembling wild-type MLV Gag protein

Summary

Introduction

I was fortunate to be associated with the lab of Stephen Oroszlan at the US National Cancer. These results confirmed that the N-terminal glycine was necessary for myristylation, and demonstrated that the myristyl modification was crucial for membrane association and virus production by the MLV Gag protein.

Results

Conclusion