Viral Replication

Overview

Here we discuss the basic molecular processes which occur during viral infection of a host cell. Although the specifics may be different for each virus, the general features of infectious cycles are the same. Below we list the steps in the order which they occur when a single virus encounters an uninfected host cell.

Attachment

Viruses must first attach to host cells and this often occurs via fairly specific molecular interactions between viral surface proteins and host cell surface molecules. Enveloped viruses attach via proteins within their envelope whereas unenveloped viruses attach via proteins of their capsid. The specific nature of viral attachment accounts for the tropism of certain viruses for particular cell types and tissues. In these cases, viral tropism occurs because only certain cells and tissues possess the surface molecules to which the virus can attach.

Penetration

Attachment of virus induces changes in both the virus and the host cell which promote penetration of the virus into the host cell. A variety of mechanisms may account for viral entry and penetration may occur directly through the plasma membrane or through the membrane of endosomes following endocytic internalization of the viral particle. Whatever the case, the end result of penetration is the entry of the viral capsid into the host cell's cytosol.

Uncoating

Upon entry into the cytosol, the viral capsid must release its internal viral genome. This process is known as uncoating and allows the viral genome to directly access the host cell's molecular machinery.

Replication

Upon entering the host cell the virus must accomplish two basic tasks: Replication of the viral genome and synthesis of viral structural proteins. Because the composition and arrangement of the viral genome may be substantially different from that of the host cell's, complex molecular steps may be required to both replicate the viral genome and translate viral structural proteins. Many steps may require enzymes not normally present in host cells and thus must be provided by the virus. These specialized replicative viral enzymes are often the targets of antiviral therapeutics. Although the specific steps are unique to each virus some basic features exist for different genomic categories of viruses as described below.

Because host cells possess much of the machinery for DNA replication, DNA viruses are often replicated in the nucleus using a mixture of host and viral proteins. Transcription of viral structural proteins into mRNA occurs using the DNA viral genome and proceeds along lines highly similar to host genes.

Positive stranded RNA genomes can be directly recognized by host ribosomes which translate viral structural proteins as well as an RNA-dependent RNA polymerase. This RNA polymerase then synthesizes a full-length negative stranded copy of the genome which is then used as a template to replicate positive stranded viral genomic copies.

The genomes of negative ssRNA viruses are packaged with an RNA-dependent RNA Polymerase. This RNA polymerase uses the negative stranded genome as a template to synthesize positive stranded mRNAs for viral structural proteins. It also synthesizes a full-length positive-stranded copy of the genome which is then used as a template to replicate negative stranded genomic copies.

The genomes of dsRNA viruses are packaged with an RNA-dependent RNA polymerase. This RNA polymerase uses the dsRNA genome to transcribe mRNAs of viral structural proteins as well as full-length copies of the dsRNA genome.

Retroviruses are packaged with Reverse Transcriptase, an enzyme which can synthesize DNA from RNA. Reverse Transcriptase synthesizes a DNA copy of the retrovirus RNA genome and this DNA copy subsequently integrates within the host genome. The integrated viral genome then directs transcription of mRNAs encoding viral structural proteins as well as a polymerase which can synthesize fresh copies of the viral RNA genome.

Assembly and Egress

Assembly of the virus involves packaging of the viral genome with the viral core proteins as well as the surrounding capsid. Nonenveloped Viruses generally egress from host cells by lysing the cells. Enveloped Viruses generally egress from host cells by budding in which the envelope is derived from the host plasma membrane as the virus is shed.

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