ABSTRACT

Looking at the literature, pseudotyped viruses can be found as

early as in the seventies. In 1978, Zavada et al.1 described the

use of pseudotype particles as a sensitive assay for the detection

of neutralizing antibodies (N-Abs), in particular for antigens from

noncytopathogenic or slow-growing viruses.2 At that time, the so-

called pseudoparticles, or phenotypically mixed particles, referred

to replicative virions from doubly infected cells that incorporated

an envelope of one virus on the surface of the second one.

According to these authors, it was possible the rhabdovirus vesicular

stomatitis virus (VSV) could acquire surface glycoproteins (GPs) of

all retroviruses. This approach successfully produced pseudotype

particles from a wild range of viruses extensively used for the

detection of N-Abs. Nevertheless, there were some disadvantages,

in particular the tedious purification and characterization process,

the absence of a reporter signal for the direct observation of the

infection, and the biosafety concern related to the use of live viruses.

Research pioneered by Zavada demonstrated that retroviruses, like

human immunodeficiency virus (HIV), can rather easily incorporate

heterologous GPs from other viruses, including other viral families,

through phenotype mixing. These early observations were the

cornerstone to the subsequent design of HIV-1-based lentiviral

vector strategies.