2 Human Receptors for Retroviruses

Abstract

Interest in human retrovirus receptors has recently been given new impetus for two main reasons. First, the emergence of human immunodeficiency virus type 1 (HIV-1) as a major pathogen has fueled the search for inhibitors of retroviral replication, including the early steps in infection. Second, the utility of retroviruses as vectors for gene transfer and gene therapy is stimulating interest both in natural receptors and in artificially targeted retroviral vectors. Thus, a greater understanding of retrovirus attachment and entry will enhance two important areas of medical research.

Different types of retrovirus recognize an extraordinary variety of receptors. In recent years, some of these receptors have been molecularly defined, but the selectivity of retrovirus/receptor interactions has been known since the 1960s, on account of the specificity of host range and receptor interference properties of retroviral pseudotypes bearing different envelope glycoproteins (Weiss 1993). In initiating infection, the outer, surface (SU) envelope glycoproteins of retroviruses carry the binding sites for receptor recognition, whereas the transmembrane (TM) envelope protein is thought to effect membrane fusion. The envelope spikes visualized by electron microscopy are trimers or tetramers of SU/TM units.

A number of conformational changes occur following the initial binding to receptors before membrane fusion and internalization is achieved. These events have been studied in most detail with HIV-1, which appears to require secondary receptors accessory to the principal binding receptor, CD4, to achieve viral entry. With the C-type retroviruses that are used as gene vectors, however, there is no evidence to date for the...