Herpesviruses as Genetic Vectors

Abstract

The members of the Herpesviridae family are large, DNA-containing, enveloped viruses. Nearly 100 herpesviruses infect a broad spectrum of the animal kingdom (Roizman 1990). So far, seven different types of human herpesviruses have been described (Table 5.1). Human herpesviruses are among the largest known human viruses, with genome sizes ranging from 125 kb for the varicella-zoster virus to 229 kb for the cytomegalovirus. The herpes virions carry the viral genome as a double-stranded linear DNA. Most of the viral DNA appears as a unique coding sequence, although herpesviruses are characterized by different classes of terminal and internal repeats. The vast and complex coding capacity of the herpes genome includes proteins involved in nucleic acid metabolism and DNA synthesis, in addition to regulatory and structural proteins. For example, HSV-1 codes for 72 different proteins (Roizman and Sears 1990), while EBV has coding potential for at least 100 proteins (Kieff and Liebowitz 1990). Size variations of the herpes genomes can occur due to the variable number of repeats and spontaneous deletions, particularly with extensive passage in tissue cultures. Upon cell infection and migration of the viral genome to the host nucleus, the herpesviruses can either enter latency and be maintained as circular episomes, or pursue a lytic replication cycle with the production of virions and cell death (Figure 5.1);