Viruses

Chapter 10 Viruses


There are three essential attributes of life: a membrane that physically separates the living cell from its environment; the generation and utilization of metabolic energy; and reproduction.


Viruses have dispensed with cell structure and metabolism but are capable of reproduction. Being unable to generate the metabolic energy required for their reproduction, they depend on a living cell to replicate their nucleic acid and synthesize their proteins. Thus viruses are villains not by choice but by necessity.


All viruses are obligatory intracellular parasites. They do nothing useful for the organism that harbors them. They are encountered mainly as the causes of viral diseases. These diseases are difficult to treat because viruses are so simple that they offer few targets for drug development. This chapter introduces the lifecycles of the major types of viruses.



Viruses can replicate only in a host cell


The viral genome can be formed from any kind of nucleic acid: double-stranded DNA, single-stranded DNA, single-stranded RNA, or double-stranded RNA. Viruses are genetic paupers, with anywhere between 3 and 250 genes, in comparison with 4435 genes in Escherichia coli and 25,000 to 30,000 in Homo sapiens.


Outside the cell, the virus exists as a particle with viral nucleic acid wrapped into a protective protein coat, or capsid. Viral genomes are too small to encode large numbers of structural proteins. Therefore capsids are formed from a few proteins that polymerize into a regular, crystalline structure. The protein coat protects the nucleic acid from physical insults and enzymatic attack, and it is required to recognize and invade the host cell.


Many animal viruses are enclosed by an envelope, which is a piece of host cell membrane appropriated by the virus while it is budding out of its host cell. The envelope is studded with viral proteins, the spike proteins (Fig. 10.1).



The viral nucleic acid can be replicated only in the host cell, and host cell ribosomes are required for the synthesis of the viral proteins. Some viral proteins are enzymes for virus replication, and others form the capsid or appear as spike proteins in the viral envelope.



Bacteriophage T4 destroys its host cell


Viruses that infect bacteria are called bacteriophages (“bacteria eaters”) or simply “phages.” Bacteriophage T4 is a classic example. It is one of the most complex viruses known (Fig. 10.2), with a double-stranded DNA genome of about 150 genes tightly packed into the head portion of the virus particle. Attached to the head is a short neck followed by a cylindrical tail with two coaxial hollow tubes, a base plate, and six spidery tail fibers. This complex capsid consists of about 40 virus-encoded polypeptides, each present in many copies.



T4 is constructed like a syringe that injects its DNA into the host cell. First, the tail fibers bind to a component of the bacterial cell wall that serves as a virus receptor. Next, the sheath of the tail contracts, its inner core penetrates the cell wall, and the viral DNA is injected into the cell. Only the DNA enters the host cell. The protein coat remains outside (Fig. 10.3).



Some viral genes are transcribed immediately by the bacterial RNA polymerase. One of these “immediate-early” genes encodes a DNase that degrades the host cell chromosome. The viral DNA is not attacked by this DNase because it contains hydroxymethyl cytosine instead of cytosine.


During later stages of the infection, viral proteins substitute for the σ subunit of bacterial RNA polymerase and direct the transcription of the “delayed-early” and “late” viral genes. The promoters of these genes are not recognized by the bacterial σ subunit.


The early viral proteins include enzymes for nucleotide synthesis, DNA replication, and DNA modification. The viral coat proteins are synthesized late in the infectious cycle, and new virus particles are assembled from the replicated viral DNA and the newly synthesized coat proteins. Finally, virus-encoded phospholipase and lysozyme destroy the bacterial plasma membrane and cell wall.


This mode of virus replication is called the lytic pathway because it ends with the lysis (destruction) of the host cell. It takes approximately 20 minutes, and about 200 progeny viruses are released from the lysed host cell.



DNA viruses substitute their own DNA for the host cell DNA


Some but not all features of lytic infection by bacteriophage T4 are typical for viral infections in general:





Some enveloped viruses fuse their envelope with the plasma membrane of the host cell, whereas others trigger their own endocytosis (Fig. 10.4).








Jun 18, 2016 | Posted by in BIOCHEMISTRY | Comments Off on Viruses

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