General Virology

The viruses are a large group of obligate intracellular parasites capable of infecting a variety of different cell types. Viruses may contain either DNA or RNA as their genomic material and this material may be either single- or double-stranded. Single-stranded genomes may be of positive (i.e. mRNA) or negative (i.e. anti-mRNA) polarity. Surrounding and protecting the genome is a coat of protein ("capsid") arranged in one of several possible morphologies. Certain viruses also contain an additional phospholipid bilayer ("envelope") derived from the host cell and surrounding the protein capsid. This page will discuss the similarities and differences of these biological entities. Some of the viruses that cause disease in humans are described in the following table (or click here to see a viral classification flowchart):

The process of viral multiplication involves several discrete steps. First, the virus must recognize and attach to its host cell. Generally, viruses are limited as to the type of host cell in which they can multiply and so recognition is often very specific. Viruses adsorb to their host cell surface via specific antireceptor molecules, often glycoproteins. Adsorption is generally temperature and energy independent. Penetration into the host cell, however, is often energy dependent and may occur by three different mechanisms; 1) translocation of the plasma membrane, 2) pinocytosis into cytoplasmic vacuoles, or 3) fusion of the plasma membrane with the viral envelope. Non-enveloped viruses may enter via translocation or pinocytosis; enveloped viruses typical enter via fusion. Once inside the host cell, uncoating releases the viral genome to be replicated.

The replication scheme employed by the viruses depends upon the type of genome that each contains. The following panels describe each particular type:

	Positive-stranded RNA Viruses					Negative-stranded RNA Viruses
	+RNA (mRNA)		Proteins (replicative)			-RNA
								RDRP
	-RNA					+RNA (mRNA)		Proteins (replicative)
	+RNA		Proteins (structural)			-RNA		Proteins (structural)
	Progeny Virus					Progeny Virus
Positive-stranded RNA is essentially equivalent to mRNA and can often be immediately translated into proteins. These replicative enzymes then synthesize a negative-strand copy of the +RNA, which is then copied back into +RNA messages. Translation of these messages produces structural proteins that are used to package progeny +RNA into virions.					Negative-stranded RNA must first be converted into +RNA (mRNA) by the RNA-dependent RNA polymerase (RDRP) incorporated in the virion. The mRNA can then be translated into proteins. Replicative enzymes (RDRP) synthesize a negative-strand copy of the +RNA. Structural proteins translated from the mRNA are then used to package progeny -RNA and RDRP into virions.

	DNA Viruses					Retroviruses
		mRNA				+RNA		RNA/DNA
							Reverse Transcriptase
	Proteins (replicative)	dsDNA	Proteins (structural)			Integration into Host Genome		dsDNA
		dsDNA				+RNA		Proteins
		Progeny Virus				Progeny Virus
Most DNA viruses utilize a standard semi-conservative mode of replication. Often, the DNA is immediately transcribed by host proteins to produce mRNAs that encode virus-specific transcription factors. These factors lead to selective transcription of genes involved in DNA synthesis, and genes encoding additional transcription factors. This final set of factors produces mRNAs encoding structural proteins that enclose the newly-synthesized DNA, producing progeny virions.					Retroviruses have a unique means of replication. The viral RNA is first reverse transcribed by a viral protein (reverse transcriptase, RT) to produce an RNA/DNA hybrid duplex. RT then removes the RNA strand while synthesizing a new DNA strand to produce dsDNA, which then integrates into the host genome. From this location, progeny RNA molecules and structural proteins are combined to produce new viral particles.

A number of host defenses contribute to the prevention and/or elimination of viral infections. Nonspecific defenses include (prior to infection) anatomical barriers, viral inhibitors in fluids and tissues. Phagocytosis is somewhat variable. After infection, factors such as fever (viral replication is strongly influenced by temperature) and inflammatory processes including edema, leukocyte accumulation, local hyperthermia, reduced oxygen tension and altered cell metabolism can all act to reduce viral replication. Another important anti-viral factor is interferon. This substance is produced by an infected cell. It then reacts with other cells to i) activate an RNA endonuclease causing mRNA degradation or ii) cause phosphorylation of eIF2, essentially turning off cellular protein synthesis. Specific host defenses include antiviral antibody, which may prevent adsorption to target cells and cytotoxic T-lymphocytes, which recognize virally-infected cells and destroy them, reducing viral production.