Viral life cycle

Fig. 1 Antiviral genes inhibit virus replication at different stages of the viral life cycle. Early inhibitors prevent the establishment of the viral genome in the target cell (class I, e.g., entry inhibitors, RT inhibitors for HIV). Intermediate inhibitors prevent viral gene expression or amplification of the viral genome (class II, e.g., siRNAs, antisense RNAs). Late inhibitors prevent virion assembly or release, or inactivate the mature virions (class III, e.g., transdominant core proteins, capsid-targeted virion inactivation, CTVI). A list of antiviral genes in each class is found in Table 1...

There is potential in the anti-HIV field. Polyoxometallates of the Keggin type bind to viral envelope sites on cell surfaces and interfere with virus adsorption. Metal-chelating macrocyclic bicyclam ligands are among the most potent inhibitors of HIV ever described, and there is considerable interest in the role of Zn proteins in the viral life cycle. 

Studying the molecular recognition of hgands by native viruses and VLPs offers structural insight into the viral attachment and entry processes. Details at atomic resolution are important for our understanding of these early events during the viral life cycle [6]. Drug development benefits from this effort in order to develop entry inhibitors. 

Full-length viral RNA transcripts are processed by the host machinery prior to nuclear export however, if only processed viral RNA transcripts were exported from the nucleus, viral replication would halt. Both partially spliced and fully unspliced viral RNA transcripts must be exported from the nucleus to serve as open reading frames for proteins (Gag, Pol, and Env) that are essential for completing the viral life cycle (Figures 10.1 and 10.3). Additionally, each new viral particle must contain two copies of the fully unspliced viral RNA, which serves as the primary genome for progeny virions. 

Baculovirus expression is the most frequently used method for expression in insect cells and employs Autographa californica nuclear polyhedrosis virus (AcNPV), a double stranded (ds) DNA virus that infects arthropods. The baculovirus expression system utilizes features of the viral life cycle to introduce recombinant DNA coding the gene of interest into insect cells (Miller, 1988 O Reilly et al, 1992). 

Three regions of the picornavirus stmcture deserve special attention because they appear to play crucial roles in the viral life cycle as well as bear on the function of the capsid-binding compounds. These regions are the canyon, the VP1 hydrophobic pocket, and the [3 cylinder. 

Because viruses contain small genomes, study of transcription of viral DNA and of replication of RNA viruses has played an important role in helping us to understand transcription in eukaryotes 47/686-688 An example is the discovery of the virus SV40 enhancer, which has been discussed in Section C,4. Study of viral life cycles is also essential to future progress in fighting viral diseases. Each of the many different viruses has its own often very complex life cycle. Only a few details can be given here. For lucid summaries see Voyles.259... 

The viral protein R (Vpr) of HIV-1 plays a significant role early in the viral life cycle by facilitating the nuclear import of the preintegration complex in non-dividing cells. The C-terminal domain of Vpr (Vpr52-96), which condenses plasmid DNA, mediates DNA transfection in a variety of human and non-human cell lines (Table 16.7). The Vpr52-96 sequence... 

The number of myristoylated proteins identified in viruses is constantly increasing. Nevertheless, substantial additional work will be required to shed light on the multiple functions that could be executed by the respective proteins as well as their involvement in the viral life cycle and elucidation of the role of the lipid anchor. Inhibition of NMT or replacing myristic acid by analogs in infected cells is known to affect numerous viruses of medical importance, for example, HIV (Bryant et al. 1989), hepatitis B virus (Parang et al. 1997), herpesviruses (Harper et al. 1993), and... 

P)-Calanolide A (1) inhibited HIV-1 in cell culture but was inactive against HIV-2 or SIV. In the viral life-cycle investigations, it was demonstrated that calanolide A... 

The catalytic ability of RNA molecules is related to their ability to adopt specific yet complex structures. This principle is illustrated by a "hammerhead" ribozyme, an RNA structure frrst identified in plant viruses (Figure 2.5). This RNA molecule promotes the cleavage of specific RNA molecules at specific sites this cleavage is necessary for certain aspects of the viral life cycle. The ribozyme, which requires Mg2+ ion or other ions for the cleavage step to take place, forms a complex with its substrate RNA molecule that can adopt a reactive conformation. 

New antiviral agents have been based on virus-specific targets, especially the viral enzymes that are involved in the viral life cycle, i.e. responsible for the production of infectious viral particles. Research has focused on virus-encoded proteases that fulfil this role. Thus, specific inhibitors of HIV, herpesvirus and hepatitis C virus proteases are now known. Examples of clinically approved HIV pro-... 

The postintegrative or efferent phase of the HIV-1 life cycle also provides several attractive therapeutic targets if viral-specific factors can be identified. The recent excitement over the clinical benefit from HIV-1 protease inhibitors, which disrupt viral protein processing during the efferent phase, demonstrate the potential for intervention targeting these steps. Other attractive efferent components include viral transcription, assembly, and release. Furthermore, many cellular factors are involved in completing these steps of the viral life cycle and are potential targets of intervention if selectivity can be achieved. 

---