Virus Replication (World of Microbiology and Immunology)
Viral replication refers to the means by which virus particles make new copies of themselves.
Viruses cannot replicate by themselves. They require the participation of the replication equipment of the host cell that they infect in order to replicate. The molecular means by which this replication takes place varies, depending upon the type of virus.
Viral replication can be divided up into three phases: initiation, replication, and release.
The initiation phase occurs when the virus particle attaches to the surface of the host cell, penetrates into the cell and undergoes a process known as uncoating, where the viral genetic material is released from the virus into the host cell's cytoplasm. The attachment typically involves the recognition of some host surface molecules by a corresponding molecule on the surface of the virus. These two molecules can associate tightly with one another, binding the virus particle to the surface. A well-studied example is the haemagglutinin receptor of the influenzae virus. The receptors of many other viruses have also been characterized.
A virus particle may have more than one receptor molecule, to permit the recognition of different host molecules, or of different regions of a single host molecule. The molecules on the host surface that are recognized tend to be those that are known as glycoproteins. For example, the human immunodeficiency virus recognizes a host glycoprotein called CD4. Cells lacking CD4 cannot, for example, bind the HIV particle.
Penetration of the bound virus into the host interior requires energy. Accordingly, penetration is an active step, not a passive process. The penetration process can occur by several means. For some viruses, the entire particle is engulfed by a membrane-enclosed bag produced by the host (a vesicle) and is drawn into the cell. This process is called endocytosis. Polio virus and orthomyxovirus enters a cell via this route. A second method of penetration involves the fusion of the viral membrane with the host membrane. Then the viral contents are directly released into the host. HIV, paramyxoviruses, and herpes viruses use this route. Finally, but more rarely, a virus particle can be transported across the host membrane. For example, poliovirus can cause the formation of a pore through the host membrane. The viral DNA is then released into the pore and passes across to the inside of the host cell.
Once inside the host, the viruses that have entered via endocytosis or transport across the host membrane need to release their genetic material. With poxvirus, viral proteins made after the entry of the virus into the host are needed for uncoating. Other viruses, such as adenoviruses, herpesviruses, and papovaviruses associate with the host membrane that surrounds the nucleus prior to uncoating. They are guided to the nuclear membrane by the presence of so-called nuclear localization signals, which are highly charged viral proteins. The viral genetic material then enters the nucleus via pores in the membrane. The precise molecular details of this process remains unclear for many viruses.
For animal viruses, the uncoating phase is also referred to as the eclipse phase. No infectious virus particles can be detected during that 102 hour period of time.
In the replication, or synthetic, phase the viral genetic material is converted to deoxyribonucleic acid (DNA), if the material originally present in the viral particle is ribonucleic acid (RNA). This so-called reverse transcription process needs to occur in retroviruses, such as HIV. The DNA is imported into the host nucleus where the production of new DNA, RNA, and protein can occur. The replication phase varies greatly from virus type to virus type. However, in general, proteins are manufactured to ensure that the cell's replication machinery is harnessed to permit replication of the viral genetic material, to ensure that this replication of the genetic material does indeed occur, and to ensure that this newly made material is properly packaged into new virus particles.
Replication of the viral material can be a complicated process, with different stretches of the genetic material being transcribed simultaneously, with some of these gene products required for the transcription of other viral genes. Also replication can occur along a straight stretch of DNA, or when the DNA is circular (the so-called "rolling circle" form). RNA-containing viruses must also undergo a reverse transcription
In the final stage, the viral particles are assembled and exit the host cell. The assembly process can involve helper proteins, made by the virus or the host. These are also called chaperones. Other viruses, such as tobacco mosaic virus, do not need these helper chaperones, as the proteins that form the building blocks of the new particles spontaneously self-assemble. In most cases, the assembly of viruses is symmetrical; that is, the structure is the same throughout the viral particle. For example, in the tobacco mosaic virus, the proteins constituents associate with each other at a slight angle, producing a symmetrical helix. Addition of more particles causes the helix to coil "upward" forming a particle. An exception to the symmetrical assembly is the bacteriophage. These viruses have a head region that is supported by legs that are very different in structure. Bacteriophage assembly is very highly coordinated, involving the separate manufacture of the component parts and the direct fitting together of the components in a sequential fashion.
Release of viruses can occur by a process called budding. A membrane "bleb" containing the virus particle is formed at the surface of the cell and is pinched off. For herpes virus this is in fact how the viral membrane is acquired. In other words, the viral membrane is a host-derived membrane. Other viruses, such as bacteriophage, may burst the host cell, spewing out the many progeny virus particles. But many viruses do not adopt such a host destructive process, as it limits the time of an infection due to destruction of the host cells needed for future replication.
See also Herpes and herpes virus; Human immunodeficiency virus (HIV); Invasiveness and intracellular infection