Viruses are strict intracellular parasites, reproducing or replicating only inside a host cell. The six steps of virus replication, called the infectious cycle, proceed as follows (Figure 1).

1. Attachment, also referred to as adsorption, is the first step of the infectious cycle. It involves recognition of a suitable host cell and specific binding between viral capsid proteins (often the glycoprotein spikes) and the carbohydrate receptor of the host cell. Each type of virus specifically recognizes and attaches to a specific type of host cell, allowing infection of some tissues but not others (viral tropism, as previously described).

2. Penetration is the process by which viruses enter the host cell. One mechanism of penetration involves fusion of the viral envelope with the host cell mem brane. This method not only provides a mechanism for internalizing the virus, but also leads to fusion between the infected host cell and additional nearby host cells, forming multinucleated cells called syncytia. Detection of syncytia can be used to determine the presence of virus in cell cultures or stained smears of clinical specimens. Other mechanisms of viral penetration include phagocytosis by host cells (endocytosis) or injection of viral nucleic acid.

 3. Uncoating occurs once the virus has been internalized. It is the process by which the capsid is removed; this may be by degradation of viral enzymes or host enzymes or by simple dissociation. Uncoating is necessary to release the viral genome before the viral DNA or RNA is delivered to its intracellular site of replication in the nucleus or cytoplasm.

4. Macromolecular synthesis involves the production of nucleic acid and protein polymers. Viral transcription leads to the synthesis of messenger RNA (mRNA), which encodes early and late viral proteins. Early proteins are nonstructural elements, such as enzymes, and late proteins are structural components. Rapid identification of virus in a cell culture can be accomplished by detecting early viral proteins in infected cells using immunofluorescent staining techniques. Replication of viral nucleic acid is necessary to provide genomes for progeny virus particles or virions. Macromolecular synthesis varies, depending on the organization of the viral genome.

 5. Viral assembly is the process by which structural proteins, genomes, and in some cases viral enzymes are assembled into virus particles. Envelopes are acquired during viral “budding” from a host cell membrane. Nuclear endoplasmic reticulum and cytoplasmic mem branes are common areas for budding. Acquisition of an envelope is the final step in viral assembly.

 6. Release of intact virus particles occurs after cell lysis (lytic virus) or by budding from cytoplasmic mem branes. Release by budding may not result in rapid host cell death, as does release by cell lysis. Detection of virus in cell cultures is facilitated by recognition of areas of cell lysis. Detection of virus released by budding is more difficult, because the cell monolayer remains intact. Influenza viruses, which are released by budding with minimal cell destruction, can be detected in cell culture by an alternative technique called hemadsorption. Influenza virus–infected cells contain virally encoded glycoprotein hemagglutinins inserted into the host cell’s cytoplasmic membrane, preparing for inclusion in the viral envelope at the time of release by cytoplasmic budding. Red blood cells (RBCs) added to the culture medium adsorb to the outer membranes of infected cells but not to uninfected cells. Each infected host cell results in as many as 100,000 virions; however, as few as 1% of these may be infectious or “viable” in the practical sense. Noninfectious viral particles may result from errors or mutations that occur during the infectious cycle.

Fig1. Illustration of the viral infectious cycle. (Modified from Murray PR, Drew WL, Kobayashi GS, et al, editors: Medical microbiology, St Louis, 1990, Mosby.)

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مواضيع ذات صلة

HIV Infections in Humans: Laboratory Diagnosis

HIV Infections in Humans :Clinical Findings

HIV Infections in Humans : Pathogenesis and Pathology

Animal Lentivirus Systems

Classification of Lentiviruses

Viral DNA Is Integrated into the Host-Cell Genome in Some Nonlytic Viral Growth Cycles

Lytic Viral Growth Cycles Lead to Death of Host Cells

Viral Capsids Are Regular Arrays of One or a Few Types of Protein

Structure and Composition of Lentiviruses

HERPESVIRUSES

POLYOMAVIRUSES

Human T-Lymphotropic Viruses