Once a virus infects a cell, the infection may take one of the following courses:
  • Productive: the cells are permissive for viral replication and virion progeny are released
  • Abortive: the cells are non permissive for a viral function and virion particles not produced.
  • Restrictive: the cell is transiently permissive and a few viruses are produced. Viral production then ceases but the genome persists. Such cells may undergo transformation.
The steps in viral replication:
  1. Attachment
  2. Penetration
  3. Uncoating
  4. Nucleic acid replication
  5. Virus gene expression
  6. Virus assembly and maturation
  7. Release

Shortly after infection and for several hours, only low amounts of infectious material can be identified, this called the eclipse phase. It is a period where genome replication has been initiated but progeny viruses are not yet released. During the eclipse stage, no complete viral particles can be viewed within the cell. The reproductive cycle may vary from 6-8 hours in Picornaviruses to more than 40 hours in some Herpesviruses. Cells infected with polio can yield more than 100,000 copies of virus per infected cell. 

Infection begins when a virus binds to a specific cell receptor on the host cell. Some receptors are glycoproteins while others are phospholipids or glycolipids. For example CD4 (a protein), is the primary receptor for HIV. In many viruses, attachment leading to successful infection requires participation of a co-receptor. Each susceptible cell probably contains at least 100, 000 receptor sites for a given virus. Cells lacking specific receptors are resistant.

In case of enveloped viruses, the membrane plays an important role in penetration. It fuses with a host cell membrane releasing the virus nucleocapsid into the cell. Fusion is promoted by a virus membrane protein (e.g., hemagglutinin of Influenza virus, gp120 of Retroviruses and the F protein of Parainfluenza viruses). Fusion of virus and cell membranes may take place in some cases (as in HIV) at the cell surface membrane. In some cases, as in influenza virus, the virus is actively engulfed by the host cell by endocytosis into an endocytic vesicle. The membrane of the vesicle and viral envelope fuse, releasing the virus inside the cytoplasm of the host cell. Non-enveloped viruses can penetrate cells in two different ways: (1) by injecting the nucleic acid through the cytoplasmic membrane (as in Polio virus) or (2) through the membrane of an endocytic vesicle following receptor mediated endocytosis of the virus (as in Adenovirus).

Uncoating always occurs in the cytoplasm of the host cell. This step occurs in those viruses where the capsid or nucleocapsid enters the cytoplasm. This step is irrelevant in cases where the nucleic acid is injected into the host cell. In case of adenoviruses and Herpesviruses, once the capsid has entered the cytoplasm it migrates to the nucleus where it injects its DNA through a nuclear pore. Ultimately the viral nucleic acid is released from its capsid.

While some viruses utilize host resources for their own multiplication, others code for enzymes involved in replicative processes, e.g. Herpes simplex I and II, Varicella zoster and Cytomegalovirus all code for their own DNA polymerase. All RNA viruses (except Retroviruses) code for a viral RNA polymerase. Retroviruses have a reverse transcriptase that acts to transcribe DNA from RNA and also acts as a DNA polymerase. Early virus enzymes are often involved in DNA replication. The HSV-1 thymidine kinase and ribonucleotide reductase are examples of early virus enzymes involved in DNA replication.
In most cases, nucleic acid replication of DNA viruses takes place in the nucleus while RNA virus replication takes place in the cytoplasm. Exceptions to the above rule are: (1) the poxviruses, DNA viruses that replicate in the cytoplasm; (2) influenza viruses, RNA viruses whose replication takes place in the nucleus; and (3) retroviruses, RNA viruses replicated in the nucleus.

Replication of DNA viruses:
DNA replication in dsDNA viruses occur by a semi-conservative mechanism similar to that seen in replication of cellular DNA. Most DNA viruses code for their own DNA polymerase, whereas small DNA viruses (Parvoviruses, Papillomaviruses) do not. Commonly, one of the DNA strands is transcribed into specific mRNA, which in turn is translated to synthesize virus-specific proteins and enzymes necessary for biosynthesis of virus DNA. DNA replication can be:

  • Bi-directional, where there is simultaneous synthesis of both the leading & lagging DNA strands. E.g. Papovaviruses.

  • Replication from a linear substrate, where the synthesis of new DNA strands is not simultaneous. First one strand is made in its entirety & then the next strand is made. E.g. Adenoviruses.

  • Replication via RNA intermediate. The example of this is Hepatitis B Virus, which has a partially dsDNA genome that must be converted into an RNA form by the viral enzyme reverse transcriptase.

  • Complex replication mechanisms as in Herpes viruses.

Replication of RNA viruses
RNA viruses (such as Rabies, Ortho- and Para-myxoviruses) that are negative sense (or negative strand) carry genes for RNA polymerases to synthesize mRNAs. RNA viruses that are positive sense (such as Picornaviruses), the genomic RNA itself acts as mRNAs. Reverse transcription is the copying of RNA genome into a double stranded DNA form by an enzyme reverse transcriptase. It results in the formation of a double-stranded proviral DNA, which is transported to the nucleus and integrated into the cellular DNA.
The single-stranded RNA that is released after uncoating will act as:

  • mRNA to synthesize viral-coded proteins or

  • a template to synthesize mRNA or

  • a template to synthesize double stranded RNA, which is then used as a template to synthesize mRNA or

  • a template to synthesize double-stranded DNA, which is then utilized as a template to synthesize mRNA.

As the viral DNA continues to be transcribed, late virus functions become apparent. Messenger RNA transcribed during the later phase of infection migrates to the cytoplasm and is translated. Proteins for virus capsids are synthesized and are transported to the nucleus to be incorporated into the complete virion. Early proteins control the next phase of replicative cycle, e.g. genome replication and late protein production. Late proteins are usually structural proteins.

In most cases, virus formation takes place in the cellular compartment where the nucleic acid is replicated. For example, herpes virions are assembled in the infected cell nucleus while Picornaviruses are assembled in the cytoplasm. Retroviruses constitute an exception to this rule. Retrovirus (e.g. HIV) nucleic acid synthesis takes place in the infected cell nucleus while the virion is assembled at the cytoplasmic membrane. Assembly of the protein subunits around the viral DNA results in the formation of complete virions. After they are assembled into mature viruses, naked virions may become concentrated in large numbers at the site of maturation, forming inclusion bodies. Generally, RNA-containing naked viruses are released rapidly after maturation and there is little intracellular accumulation; therefore, these viruses do not form predominant inclusion bodies. On the other hand, DNA-containing naked icosahedral viruses that mature in the nucleus do not reach the cell surface as rapidly, and are released when the cells undergo autolysis. Thus, they generally produce highly visible inclusion bodies.

In many negative-strand RNA viruses (e.g., Orthomyxoviruses, Paramyxoviruses, and Rhabdoviruses), the RNA condenses with nucleo-protein as the RNA is synthesized. The RNA is never found separately from protein. In case of Picornaviruses, Flaviviruses, and Papillomaviruses the nucleic acid condenses with oligomers of the capsid protein to create a protein shell that ultimately surrounds the RNA or DNA. In Herpesviruses and Reoviruses the nucleic is packaged into a pre-formed, nucleic acid-free capsid.

Virus membranes are acquired by budding in the cytoplasm. Budding can occur through the cytoplasmic membrane (e.g. Influenza virus) or through organelle membranes. Many enveloped viruses are released from the host cell as the virus nucleocapsid buds through the cytoplasmic membrane. In such cases, envelopment and release of virus from the host cell occur at the same time. Paramyxo- and Orthomyxo- viruses escape from binding to their original receptor by encoding neuraminidase enzymes allowing the virus to exit the cell. Non-enveloped viruses are released by lysis of the host cell.

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   Last edited in June 2006