Across the Hall from Pioneers

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.

Keywords: HIV; post-translational modifications; retroviruses; translational suppression; viral proteins; virus maturation.

Figure 1

Syncytium Formation Induced by Expression of R- MLV Env. HEK 293T cells were transfected with a plasmid directing the expression of R- Env (A,B) or wild-type Env (C). Forty-eight hours later on’mouse cells were added to the cultures. The cultures were fixed and stained 3½ (A) or 24 (B,C) after addition of mouse cells (from ref. [48]).