Defective viral particles

Pis act by impeding the action of the HlV-1 protease, an aspartic protease that cleaves the gag and gag-pol precursor molecules into smaller structural proteins and enzymes. By doing this. Pis prevent viral maturation and produce defective viral particles without an electrodense core, and these are unable to infect new cells. Several pharmacological properties of Pis are presented in Table 41.5. 

Retrotransposons lack an env gene and so cannot form viral particles. They can be thought of as defective viruses, trapped in cells. Comparisons between retroviruses and eukaryotic transposons suggest that reverse transcriptase is an ancient enzyme that predates the evolution of multicellular organisms. 

The reproductive cycle of viruses may take hours or days. The infection of cells does not guarantee the production of viral progeny, which may be productive, restricted, aborted, or latent. A productive infection occurs in permissible cells and results in infectious viral particles. An abortive infection may occur in two circumstances firstly, although the cell is sensitive to infection, it is not necessarily permissive, allowing the expression of only a few viral genes. The second circumstance is when a sensitive cell, permissive or not, is infected by defective viruses that do not have all the necessary viral genes for their replication. Furthermore, the cells can be temporarily permissible. In this case, the viral particles may remain in the cells until they become permissive or else some viral particles may be... 

Figure 3 Differences between phage and phagemid. An example is presented. A phage vector retains all the functions and capability of forming viable viral particles. A phagemid vector is a defective phage that usually contains an antibiotic resistance gene and the E. coli origin of replication it replicates in E. coli as a plasmid and forms viable viral particles only in the presence of a helper phage. See text for more details.

Jacobson, S., and Pfau, C. J., 1980, Viral pathogenesis and resistance to defective interfering particles, Nature London) 283 311. 

The envelope glycoproteins of wild-type retroviruses and lentiviruses bind to cell surface receptors to facilitate entry of the vims into the cytoplasm where the viral RNA is reverse transcribed to form a cDNA, the proviras. This provirus is translocated to the nucleus where it integrates into the host cell chromosomes and through the normal process of DNA transcription encodes new viral proteins and new viral RNA, which are assembled at the cell surface into new viral particles. Replication-defective retroviral and lentiviral vectors infect cells by similar mechanisms, but unlike wild-type viruses, the integrated provirus from these vectors encodes the therapeutic gene and viral particles are not produced. 

Drugs known as integrase inhibitors and maturation inhibitors are also in development. Integrase inhibitors are designed to interfere with the integration of the viral genome while the maturation inhibitors specifically block the conversion of the HlV-1 capsid precursor, CA-SPl (p25) to mature capsid protein (p24). This blocking will result in defective core condensation and the release of noninfectious virus particles. 

Aston-Jones and Card, 2000 Husak et al., 2000 Kelly and Strick, 2000) as virus particles. The foreign genes they express can, therefore, be used as markers for neuronal connections. This property is not shared by rAAV particles, which are completely defective for viral replication. 

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