Distinguish early and late gene expression in virus
Answers
b) to be packaged into virions as new virus genomes. Like DNA viruses, many RNA viruses have both "early" and "late"phases of gene expression, with regulatory proteins being synthesized early and structural proteins late. ... The entire viral RNA is then translated into a single "polyprotein" using the host cell ribosomes.
Answer:
Understanding these virus/cell interactions can be important in treating and/or preventing disease. For example, antibodies that bind to the viral attachment molecule or to the cellular receptor can disrupt the normal interactions and prevent the first steps of the viral life cycle, thereby preventing infection. This is an important consideration in the development of vaccines.
II: Penetration:
Once bound to the cell membrane, the virus, or at least its nucleic acid, must enter the cell. Animal viruses do this primarily by one of two mechanisms.
Endocytosis: Many viruses enter cells via receptor mediated endocytosis . In this pathway, viruses bind to receptors at coated pits. The coated pits pinch off to form coated vesicles, which are uncoated and then fuse with endocytic vesicles, and eventually with lysosomes. As they go through this process, the endosomesbecome more acidic (remember lysosomes are a very acidic environment where the breakdown of cellular macromolecules occurs). Viral genomes must therefore escape the endosome before they are destroyed by proteases, nucleases, etc. For enveloped viruses, this usually occurs by membrane fusion mediated by a fusion protein. One example of this is the influenza virus HA protein, which undergoes a conformational change induced by the acidic environment of the endosome. After undergoing this change, it then induces membrane fusion, releasing the nucleocapsid into the cytoplasm. The genomes of non-enveloped viruses must also somehow escape the endosome. Again, this is often initiated by a conformational change in a capsid protein induced by the acidic environment of the endosome. In the case of poliovirus (a picornavirus), the capsid proteins undergo a conformational change that allows a hydrophobic domain on VP4 to be exposed and inserted into the membrane, forming a channel through which the RNA enters the cytoplasm.
Direct Membrane Fusion: Some enveloped viruses directly fuse with the plasma membrane. In these cases the activity of a fusion protein is not dependent on pH change, but rather is induced in response to receptor binding.
III: Uncoating and Targeting
With some viruses, the genome is completely released from the capsid during or after penetration. This is known as "uncoating". In others, such as retroviruses and reoviruses, the first stages of the viral replication cycle (transcription, replication) actually occur inside the capsid. These capsids have undergone some conformational changes during infection that allow viral gene expression and/or replication to begin, and the resulting structures are sometimes known as partially uncoated particles. Since almost all DNA viruses replicate in the nucleus of infected cells, they must be targeted there. In many cases the entire nucleocapsid enters the nucleus, where uncoating then takes place.
IV: Gene Expression and Genome Replication
In order for new virus to be assembled, both new viral genomes and other virion components (proteins) must be produced. Exactly how this occurs varies greatly depending on the family (and Baltimore Class) of virus. Summaries of common schemes are given below, and several specific viruses will be discussed in detail later in the semester.
Viruses with DNA Genomes:
Almost all DNA viruses have genomes that are similar to the host cell; that is, they are composed of double stranded DNA, and are therefore able to utilize host enzymes to express viral genes and replicate viral DNA. Most DNA viruses replicate in the cell nucleus, which is where cellular replication and transcription proteins are localized. After infection, the nucleocapsid of DNA viruses is therefore usually delivered to the nucleus where uncoating occurs. An exception is poxviruses, which replicate in the cytoplasm of infected cells.
A) Viruses with Small, Double Stranded DNA genomes.
Some of the best studied virus families fall into this group, including the Papovaviridae (simian virus 40, murine polyoma virus, bovine papilloma virus). Because of their relatively small genome size (5 - 10 kb), the facts that they can grow in tissue culture and use mostly cellular molecules to transcribe and replicate their DNA, these viruses have been used as model systems to study both viral replication and mammalian gene expression and DNA replication. For these simple DNA viruses, the replication cycle can be broken down into the following steps.
1) Early gene expression. The first stage in the viral replication cycle is expression of the viral early genes. Transcription of these genes occurs using cellular RNA polymerase II and cellular transcription factors.