Virus Infection Associated Proteins


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 Virus Infection Associated Proteins Background

There are many critical interactions between a virus and host cell during the course of viral infection. These interactions include those that restrict and those that facilitate completion of the viral life cycle, and identification of host cell factors involved provides valuable information on the cell biology and virology of viral infection. Creative Biomart provides varieties of molecular tools to help your virus infection applications.

 

Positive-sense RNA virus life cycle

The nucleic acid contained within a virus can take one of seven different forms, including RNA or DNA, single (ss) or double-stranded (ds), and a positive or negative polarity in the case of ssRNA viruses. The ssRNA virus group contains the most members, and among the ssRNA viruses, the positive sense RNA viruses are the most numerous. The following section outlines the general life cycle of positive sense RNA viruses, and includes the steps of viral entry, genome release, genome translation and replication, virus assembly, maturation, and egress.

Positive sense RNA viruses have small genomes encoding a limited number of proteins, thus they rely on many host cell factors throughout their life cycle. A schematic of the general life cycle of positive-sense RNA viruses is shown in Figure 1. Viral attachment and entry involves the engagement of host cell surface molecules with viral surface proteins, resulting in direct fusion and uncoating at the membrane of some enveloped viruses, or receptor-mediated endocytosis of non-enveloped and some enveloped viruses.

Positive-Sense RNA virus life cycle

Figure 1. Positive-Sense RNA virus life cycle.

Following entry, the positive sense RNA contained within the viral capsid is released into the cytoplasm of the host cell. Like viral entry, genome release requires a set of host cell endocytic trafficking proteins. Genome release is commonly accomplished through fusion of the incoming virus-containing endocytic vesicle with lower pH-containing early/late endosomes, thus triggering pH-dependent conformational changes in viral proteins to allow genome escape by either membrane fusion (enveloped viruses) or disruption of the endosomal membrane (non-enveloped viruses). From early endosomes to late endosomes/lysosomes the pH of the compartment lowers progressively to a pH of 5.0. Therefore, the stage of post-entry endocytic trafficking from which a particular viral genome escapes its vesicle depends on its individual pH requirement.

Once the RNA has reached the cytoplasm direct translation of the positive sense genome occurs. This step relies almost exclusively on the host cell translation machinery since the polarity of viral positive-sense RNA mimics the mRNA of the host cell. RNA viruses whose genome lacks the usual 5’ terminal cap and 3’ poly-A tail of host cell mRNA utilize a variety of different strategies to hijack the host cell translation machinery, including utilization of an internal ribosome entry site (IRES) in the 5’ untranslated region of the RNA for recruitment of the ribosome. Whereas host cell mRNA molecules are monocistronic (meaning they encode for only one functional protein each) most viral RNA molecules are polycistronic. This allows for more efficient protein production from a limited genome. An example of this is illustrated by the picornaviruses. Translation of the picornaviral RNA is initiated by ribosome binding at the IRES, resulting in the translation of a polyprotein containing all viral proteins. The polyprotein is then cleaved into individual functional proteins by two viral proteases.

Once the production of viral proteins has begun, replication of the viral RNA can commence. This is because the host cell does not normally produce RNA from an RNA template, and therefore the host cell does not contain the correct polymerase to achieve this (an RNA-dependent RNA polymerase, or RDRP). Thus, viral RNA replication cannot begin until the RDRP has been translated. There are host cell proteins involved in the active replication of positive-sense RNA viruses. For example poliovirus (PV) requires the host protein poly (rC) binding protein for initiation of replication. However, many of the host cell factors required for positive-sense RNA virus replication are the membranes and lipids that provide the scaffolding and protection for the viral replication complex.

The last steps in the viral life cycle include assembly of the progeny virions followed by their maturation and release. During assembly of the progeny virions the viral structural proteins are assembled into a viral capsid structure and the newly replicated viral RNA packaged inside it to produce new virions, which often takes place at or near host cell-derived membranes. In some cases, the newly assembled virion must undergo a maturation process prior to becoming a fully infectious viral particle. An example of this is illustrated by PV. Cleavage of structural protein VP0 into VP2 and VP4 is required for a fully mature and infectious PV particle to be released. In other cases the acquisition of a viral envelope from the host cell membranes constitutes part of the maturation process. Viral egress is a diverse process among positive-sense RNA viruses, and includes the cytopathic event of host cell lysis to allow release of viral particles (as for most non-enveloped viruses such as poliovirus), viral hijacking of the host exocytic pathway, or budding from the membrane in the case of viruses that assemble at the plasma membrane. During all of these different exit strategies the virus relies heavily on host cell factors to achieve release of the mature infectious virus particle.