疾病及处理

It is critically important that new therapeutic compounds and targets for therapeutic intervention be identified in the battle against the human immunodeficieny virus type 1(HIV-1). Many of the currently existing therapeutic approaches target virus-specific factors involv ...

This chapter describes the procedures that can be used to determine compounds that have antiviral activity against HIV. These include: maintenance of lymphoblastoid cell lines, preparation of peripheral blood mononuclear cells (PMMCs), and determination of the infectivity of the ...

When evaluating potential antiviral compounds, determining the effect of the drug on virus replication is usually the prime concern. However, since virus replication is dependent on the host cell, in circumstances where virus infection is not rapidly lytic to cells, the effect of these com ...

The high replication rate of HIV, together with the low fidelity of its reverse transcriptase, provides the virus with an unprecedented genomic flexibility. This allows a fast adaptation to selective pressure, including antiviral drugs, resulting in the development of drug-resista ...

The human immunodeficiency virus type 1 (HIV-1) belongs to the family of positive-stranded, enveloped RNA viruses with a DNA intermediate step (retroviruses). Because of the lack of fidelity of the reverse transcriptase (RT), the replication is error-prone, and the infection is characte ...

HIV, the etiologic agent of AIDS, is a retrovirus of the family Lentiviridae, first isolated in 1983 by the group of Luc Montagnier at the Pasteur Institute of Paris (1). In the following years, much effort has been, and still is, focused on the search for antiviral drugs that would help to control the course of the ...

Reverse transcriptase (RT) has attracted particular attention as a target enzyme for AIDS chemotherapy, because the enzyme catalyzes a crucial step in the HIV replicative cycle. Effective inhibition of this enzyme prevents the formation of proviral DNA. RT is endowed with three indepen ...

Retroviruses are widely prevalent among vertebrates and are the causative agents of a variety of diseases in humans and animals including immunodeficiences, leukemias, and lymphomas (1). The retrovirus family is characterized by the presence of virion-associated reverse trans ...

All replication-competent retroviruses possess a characteristic enzyme, reverse transcriptase (RT), which is present at 20–70 mol/virus particle (1–3). The enzyme is cleaved, and thereby activated, from an inactive precursor by the action of another retroviral enzyme, the viral pro ...

HIV protease catalyzes the hydrolysis of specific peptide bonds of viral polyproteins, thus processing these polyproteins into their active components. These protein processing reactions are requisite for viral replication. Therefore, the HIV protease is an ideal target for the c ...

Two critical events are the signature of the life cycle of retroviruses (1). The first is reverse transcription, whereby the single-stranded RNA genome of the retrovirus is copied into double-stranded DNA. The second of these events is integration, whereby this viral DNA is inserted into a chro ...

Papillomavirus genomes replicate and are maintained as stable extrachromosomal plasmid DNA (episomes) in many cell lines (reviewed in ref. 1). This process requires the viral E1 and E2 proteins and the origin of replication (2,3). The minimal origin of replication consists of an E1 binding si ...

Human papillomaviruses (HPV) comprise a genus in the species Papovaviridae, which consist of small, naked icosahedral viruses containing circular dsDNA. HPV types 16 and 18 infect squamous epithelium of the genitalia and may infect as many as 45% of the female population in developed count ...

Viruses that are less sensitive to the influenza neuraminidase (NA)-specific inhibitor 4-guanidino-Neu5Ac2en (zanamavir) (1) can be isolated after several passages in MDCK cells in the presence of the inhibitor. Although there are three reports of a mutation in the NA gene at the same conse ...

The compound 4-guanidino-Neu5Ac2en (zanamivir) has been described as a selective inhibitor of the influenza virus neuraminidase (NA) (1). Viruses that are less sensitive to this inhibitor can be isolated after several passages in MDCK cells in the presence of the inhibitor. Variants iso ...

The last decade has seen a remarkable flourishing of the biological structure field. This blossoming has brought an explosion of stereochemical information, and has been made possible by the combined improvement in techniques of X-ray crystallography, nuclear magnetic resonance ( ...

Since the herpes simplex virus type 1 (HSV-1) genome has been sequenced and most HSV-1 RNAs are not spliced (1), detailed information about the structure of many HSV-1 RNAs can be obtained without the considerable time and effort that is required to construct and analyze cDNA libraries. Once the 5′ and 3′ e ...

During lytic virus replication, herpes simplex virus (HSV) exhibits a closely regulated pattern of viral gene expression and of DNA replication, resulting in virion production (1). Broadly, HSV genes can be divided into immediate early, early, and late categories based on the kinetics of the ...

Investigations of genome replication in DNA viruses involve several facets. These include characterizing the sites at which synthesis is initiated (origins of DNA replication), identifying the viral and host proteins that participate, understanding the enzymatic activities ...

Herpes simplex virus (HSV) amplicons are defective virus vectors capable of introducing amplified foreign genes into variable types of eukaryotic cells, such as fibroblasts, macrophages, glia, and neurons in different organisms including rodents, monkeys, and human (refs. 1–3; rev ...