"MICROBIAL DIVERSITY & ECOLOGY"
What Is a Virus?
The discovery of mimivirus, a giant virus that infects the amoeba Acanthamoeba polyphaga and other megaviruses, has renewed a debate among biologists, chemists, virologists, and others:
Are viruses alive?
It has also introduced a new level of complexity to this debate:Vidyanand jha
However, there are others they lack: metabolic capabilities, especially energy-conserving processes, and an ability to carry out any of the processes associated with life outside a host cell.
Another shift in thinking about viruses occurred when Wendell Stanley (1904–1971) and colleagues (all chemists) crystallized tobacco mosaic virus virions. The fact that they could be crystallized caused many to begin thinking of viruses simply as complexes of chemicals, rather than as biological entities.
The large size and coding capacity of megaviruses and the surprising discovery that they need not rely totally on their hosts for translation have fueled the debate. Indeed, the genomes of megaviruses are extensive enough to support the replication of their own viruses.
In other words, some megaviruses are parasitized by viruses called virophages. Virophages use megavirus-encoded enzymes to complete their multiplication cycles.
Surprisingly, one virophage genome is integrated into its megavirus “host.” In 2008 Didier Raoult and Patrick Forterre formalized their thoughts about what makes a virus a virus in a paper they published in Nature Reviews Microbiology.
They proposed, first of all, that viruses are living organisms. They then argued that organisms should be divided into two groups: those that synthesize translational machinery (i.e., cellular organisms) and those that synthesize capsid (i.e., viruses).
As you might imagine, this has caused considerable controversy. These giant viruses have generated other controversies. Some scientists suggest that megaviruses be included in the tree of life as the fourth domain. Others argue that megaviruses may have given rise to the nucleus during the evolution of eukaryotic cells.
There is also much debate about when and how megaviruses arose. Don’t be surprised if more controversies arise as more is learned about these viruses.
What makes a virus a virus?
The confusion and debate stem from several sources. The first is that biologists have difficulty defining life. Instead, biologists have a list of attributes associated with life. Viruses share some of those attributes: they multiply, they evolve, they alter their gene expression in response to environmental stimuli (e.g., induction).Vidyanand jha
So far our discussion of dsDNA viruses has focused on bacteriophages and archaeal viruses. We now turn our attention to some important dsDNA viruses of eukaryotes, beginning with herpesviruses.
As you will see, the life cycle of these viruses shares many features with that of bacteriophages such as T4. However, important distinctions in the life cycles exist because of the nature of their respective host cells. Herpesviruses are members of the order Herpesvirales.
This order includes herpes simplex virus type 1 (HSV-1; also called human herpesvirus 1)
herpes simplex virus type 2 (HSV-2; also called human herpesvirus 2), which cause cold sores and genital herpes, respectively (see figures);
varicella-zoster virus (also called human herpesvirus 3), which causes chickenpox and shingles (see figures)
cytomegaloviruses (species Human herpesvirus 5)
Epstein-Barr virus (also called human herpesvirus 4), which causes infectious mononucleosis and has been implicated in some human cancers
HHV 8 (species Human herpesvirus 8), the cause of Kaposi’s sarcoma in AIDS patients
- Genital herpes (section 38.3)
- Chickenpox (varicella) and shingles (herpes zoster) (section)
- Cytomegalovirus inclusion disease (section)
- Mononucleosis (infectious) (section)
- Acquired immune deficiency syndrome (AIDS) (section)
Herpesvirus virions are 125 to 200 nm in diameter, somewhat pleomorphic, and enveloped (See Figure). The envelope contains distinct viral projections (called spikes) that are regularly dispersed over the surface.
The envelope surrounds a layer of proteins called the tegument (Latin, tegumentum, to cover), which in turn surrounds the nucleocapsid. Herpesvirus genomes are linear, about 125 to 295 kilobase pairs (kb) long, and encode 70 to over 200 proteins.
When herpesviruses target cells of vertebrate hosts, some bind to epithelial cells, others to neurons. Host cell selection is mediated by the binding of envelope spikes to specific host cell surface proteins termed receptors. Herpesviruses cause both productive infections and latent infections.
In a productive infection, the virus multiplies explosively; between 50,000 and 200,000 new virions are produced from each infected cell. As the virus multiplies, the host cell’s metabolism is inhibited and the host’s DNA is degraded. As a result, the cell dies.
The first exposure to a herpesvirus usually causes this type of infection. Some of the cells infected in the initial infection develop a latent infection. During the latent infection, virions cannot be detected. However, the virus can be reactivated in the host cells, leading to a productive infection.
The viral genome remains in the host cell after reactivation; thus once infected, the host can experience repeated productive infections.
A productive infection caused by HSV-1 is shown in figure. It begins with receptormediated attachment followed by fusion of the viral envelope with the host cell membrane. The initial association is between proteoglycans of the epithelial cell surface and viral glycoproteins.
This is followed by a specific interaction with one of several cellular receptors. The nucleocapsid and some associated tegument proteins are released into the cytoplasm and transported by the host cell’s microtubule/dyenin system to the nucleus.
The linear dsDNA and some of the tegument proteins then enter the nucleus by way of a nuclear pore complex. Immediately upon entry of the viral DNA into the host nucleus, the DNA circularizes and is transcribed by host DNA-dependent RNA polymerase to form mRNAs, which are translated to yield several immediate early and early proteins.
These are mostly regulatory proteins and enzymes required for replication of viral DNA (figure steps 1 and 2). Replication of the genome with a virus-specific DNA-dependent DNA polymerase begins in the cell nucleus within 4 hours after infection (figure 27.16, step 3). Viral structural proteins are the products of the late genes.
These proteins enter the nucleus, where they are assembled into nucleocapsids. Capsid formation and genome packaging are similar to that seen for bacteriophage T4. The acquisition of the tegument and envelope, and exit from the host cell are interesting processes that require several steps to complete.
Once the nucleocapsid is assembled, it makes contact with the inner membrane of the nucleus. It then buds into the space between the two nuclear membranes. This generates an envelope that is called the primary viral envelope.
The primary envelope is lost when it fuses with the outer nuclear membrane, releasing the herpesvirus nucleocapsid into the cytoplasm. At this point in the life cycle, some tegument proteins associate with the nucleocapsid. Additional tegument proteins are added when the developing virion is enveloped by membranes of either the Golgi apparatus or endosomes.
This yields a mature enveloped virion that is transported to the plasma membrane in a membrane vesicle. The membrane vesicle fuses with the plasma membrane and releases the mature virion from the host cell. Thus unlike many other enveloped viruses, the source of the HSV-1 envelope is an organelle membrane, rather than the plasma membrane.
Just as the life cycle of l has been of interest as a model of regulatory processes, so too has the establishment of latency by herpesviruses. It appears that both viral and host proteins play a role in establishing a latent HSV-1 infection.
Several studies have demonstrated that in epithelial cells, where productive infections occur, an HSV-1 protein called VP16 and a host protein called simply host cell factor (HCF) enter the nucleus with the viral genome. VP16 and HCF are needed for full expression of the virus’s immediate early genes.
However, VP16 and HCF do not enter the nucleus of infected neurons, and the expression of many immediate early genes is decreased. In addition, small noncoding RNAs produced by the virus further decrease expression of immediate early genes needed for a lytic infection.
The inhibition of early gene expression helps establish latency. Interestingly, the production of VP16 in virus-infected neurons is an early event in the reactivation of the virus.
Nucleocytoplasmic Large DNA Viruses (Megaviruses)
Nucleocytoplasmic large DNA (NCLD) viruses are viruses of eukaryotic cells that are thought to have arisen from a common ancestor; a new virus order, Megavirales, has been proposed to encompass them.
NCLD viruses, now often referred to as megaviruses, have similar life cycles in which most, if not all, of the events occur in the cytoplasm of their hosts. Most have large icosahedral capsids that enclose a lipid membrane.
At the center of their virions is a large dsDNA genome (compare the 10-kilobase genome of an influenza virus to the 100- to 1,200-kilobase genomes of megaviruses). Thus both the virion itself and the genome are large, often rivaling the sizes of small bacteria and their genomes. Megaviruses infect a variety of eukaryotic hosts, including animals, algae, and protozoa.
The large genomes of megaviruses enable them to encode many proteins. Thus they are very self-sufficient and rely on their hosts for much less than do other viruses.
They generally encode all the proteins needed for DNA replication, enzymes involved in recombination, RNA polymerases and associated transcription factors, and chaperone proteins. In addition, they encode some components of the translational machinery (tRNAs and aminoacyl-tRNA synthetases). Indeed, their coding capacity and size have led many virologists to rethink the definition of viruses and cells.