Virology Int-24 PDF: Introduction to Virology

Virology An Introduction Dr. Aymen Samir Yassin  Virology … Many infections of humans, animals, and plants are caused by (noncellular) agents: viruses. Viruses cause many of the diseases that are very common around the world: the common cold, influenza, and AIDS, to name a few. And now Cor...

Virology An Introduction Dr. Aymen Samir Yassin  Virology … Many infections of humans, animals, and plants are caused by (noncellular) agents: viruses. Viruses cause many of the diseases that are very common around the world: the common cold, influenza, and AIDS, to name a few. And now Corona, Ebola, ZIKA, and Dengue…  Virology an Introduction General characteristics of viruses ❖ They are simple compared to a cell—lacking cell membranes. ❖ Composed of only a few organic molecules. ❖ They lack most of the characteristics of life. ❖ Viruses cannot carry out any metabolic pathway. ❖ They can neither grow nor respond to the environment. ❖ They cannot reproduce independently. ❖ They must utilize the chemical and structural components of the cells they infect to produce more molecules of viral nucleic acid and viral proteins which assemble into new viruses in order to increase their numbers. ❖ Acellular, no cytoplasmic membrane, cytosol or functional organelles. ❖ Outside the cell, known as virion.  General characteristics of viruses Composition of a virus Capsid - A virion consists of a protein coat, called a capsid, surrounding a nucleic acid core. - The capsid of a virus is composed of proteinaceous subunits called capsomeres. - Some capsomeres are composed of only a single type of protein, whereas others are composed of several different kinds of proteins. Nucleic acids - The genome of a virus may be either DNA or RNA, single stranded or double stranded. - The genome of any particular virus may be either linear or composed of several molecules of nucleic acids or circular and single. Envelop (not in all viruses) - Some virions have a phospholipid membrane called an envelope surrounding the nucleocapsid (Nucleic acid + capsid). Hosts of viruses ❖ Most viruses infect only a particular host’s cells. ❖ This specificity is due to the precise affinity of viral surface proteins or glycoproteins (ligands or spikes) for complementary proteins or glycoproteins on the surface of the host cell (receptors). ❖ Viruses may be so specific that they infect not only a particular host but also a particular kind of cell in that host. ❖ All types of organisms are susceptible to some sort of viral attack(plants, bacteria, fungi, protozoa, insects, animals). Sizes of viruses ❖Viruses are so small that only a few can be seen by light microscopy. ❖Smaller viruses have a diameter of 24 nm (10-9 m); and the largest virus is about 500 nm in diameter, which is about the diameter of many bacterial cells. Shapes of viruses There are three basic types of viral shapes: helical, polyhedral (icosahedral (20 faces)), and complex. The viral envelop - A virus with a membrane is an enveloped virion, a virion without an envelope is called a nonenveloped or naked virion. - An enveloped virus acquires its envelope from its host cell. - Other viral proteins called matrix proteins fill the region between capsid and envelope. - A viral envelope is composed of a phospholipid bilayer and proteins.(Similar to cell membrane composition NOT function) - Some of the proteins are virally coded glycoproteins, which appear as spikes protruding outward from the envelope’s surface. - An envelope’s proteins and glycoproteins often play a role in the recognition of host cells. Classification of viruses ❖ By their type of nucleic acid, presence of an envelope, shape, and size. So far, they have established families for all viral genera. ❖ Family names are typically derived either from special characteristics of viruses within the family or from the name of an important member of the family. ❖ Picornaviridae contains very small RNA viruses, and Hepadnaviridae contains a DNA virus that causes hepatitis B.  Viruses Cells Inert macromolecules outside of a cell but Metabolize on their own become active inside a cell Do not divide or grow Divide and grow Acellular Cellular Obligate intracellular parasites Most are free living Contain either DNA or RNA, with few Contain both DNA and RNA exceptions Genome can be dsDNA, ssDNA, dsRNA, Genome is dsDNA or ssRNA Usually ultramicroscopic in size, ranging from 200 nm to 12 cm in diameter 10 nm to 500 nm Have a proteinaceous capsid around Surrounded by a phospholipid membrane genome; some have an envelope around the and often a cell wall capsid Replicate in an assembly-line manner using Self-replicating by asexual and/or sexual the enzymes and organelles of a host cell means Replication of animal viruses Animal viruses have five basic steps in their replication: 1- Attachment, 2- Entry, 3-Synthesis, 4-Asembly, and 5- Release. 1- Attachment Attachment of an animal virus is dependent on the chemical attraction and exact fit between proteins or glycoproteins on the virion (ligands) and complementary protein or glycoprotein receptors on the animal cell’s cytoplasmic membrane. 2- Entry Animal viruses enter a host cell shortly after attachment. Three different mechanisms: A-Direct penetration B- Membrane fusion C-Endocytosis Uncoating The removal of a viral capsid (or capsid and envelope) within a host cell is called uncoating. DNA viruses typically enter the nucleus, whereas most RNA viruses are replicated in the cytoplasm 3- Synthesis of Nucleic acids Capsomers proteins Depends on the formation of functional mRNA known as (+ mRNA) that binds to the ribosomes (of the cell) and can be translated into proteins (of the virus). functional mRNA is known as (+ mRNA): mRNA that can be translated correctly by the ribosomes. 4- Assembly Once the components of animal viruses are synthesized, they assemble into virions that are then released from the host cell. Most DNA viruses assemble in and are released from the nucleus into the cytosol. Most RNA viruses develop solely in the cytoplasm. The number of viruses produced and released depends on both the type of virus and the size and initial health of the host cell. 5- Release Enveloped animal viruses are often released via a process called budding. As virions are assembled, they are extruded through one of the cell’s membranes— the nuclear, endoplasmic reticulum, or the cytoplasmic membrane. Each virion acquires a portion of membrane, which becomes the viral envelope. During synthesis, some viral glycoproteins are inserted into cellular membranes, and these proteins become the glycoprotein spikes on the surface of the viral envelope. Naked animal viruses may be released in one of two ways: Either they may be extruded from the cell by exocytosis, in a manner similar to budding but without the acquisition of an envelope, or they may cause lysis and death of the cell. Latency of Animal Viruses ❖Some animal viruses, including chicken pox and herpes viruses, may remain dormant in cells in a process known as latency. ❖The viruses involved in latency are called latent viruses or proviruses. ❖Latency may be prolonged for years with no viral activity, signs, or symptoms. The role of virus in cancer ❖Viruses cause 20% to 25% of human cancers in several ways. ❖Some viruses carry copies of oncogenes as part of their genomes. ❖Other viruses promote (activate) oncogenes already present in the host or interfere with normal tumor repression when they insert themselves (as proviruses) into repressor genes (destroy the repressors). Culturing viruses in the lab A- Chicken eggs Chicken eggs are a useful culture medium for viruses because they are: - Inexpensive - among the largest of cells - free of contaminating microbes - contain a nourishing yolk (which makes them self-sufficient). Most suitable for culturing viruses are chicken eggs that have been fertilized and thus contain a developing embryo. Embryonic tissues (called membranes) provide ideal inoculation sites for growing viruses. B- Cell culture Viruses can also be grown in cell culture, which consists of cells isolated from an organism and grown on the surface of a medium or in broth. Such cultures became practical when antibiotics provided a way to limit the growth of contaminating bacteria. Cell culture can be less expensive than maintaining research animals, plants, or eggs, and it avoids some of the moral problems associated with experiments performed on animals and humans. Cell cultures are of two types: Diploid cell cultures are created from embryonic animal, plant, or human cells that have been isolated and provided appropriate growth conditions. The cells in diploid cell culture generally last no more than about 100 generations (cell divisions) before they die. Continuous cell cultures are longer lasting because they are derived from tumor cells. One of the more famous continuous cell cultures is of HeLa cells, derived from a woman named Henrietta Lacks, who died of cervical cancer in 1951. C- Intact animals Rats, mice, guinea pigs, rabbits, pigs, and primates have been used to culture and study animal viruses. However, maintaining laboratory animals can be difficult and expensive, and this practice raises ethical issues for some. Viroids Are extremely small, circular pieces of RNA that are infectious and pathogenic in plants. Viroids are similar to RNA viruses except that they lack capsids. Prions Proteinaceous infective particles. Prions are not viruses because they lack any nucleic acid. How can they carry the information required to replicate them is a major question investigated by scientists. Prions are associated with several diseases, including bovine spongiform encephalitis (BSE, so-called mad cow disease), scrapie in sheep, and variant Creutzfeldt-Jakob disease (vCJD) in humans.  Antiviral Drugs Mechanism of Action Examples Attachment inhibitors - Arildone or neutralizing antibodies (antagonists) Viral uncoating inhibitors - Amantadine, Rimantadine Nucleic synthesis - DNA polymerase inhibitors: Acyclovir, inhibitors Gancyclovir - RNA polymerase inhibitors: Sofosbuvir - Reverse transcriptase inhibitors: Lamivudine, Nevirapine Protease inhibitors - For HIV: saquinavir, ritonavir - For HCV: Grazoprevir, Simeprevir Viral release inhibitors Oseltamivir, Zanamivir Interferons Alpha interferon, Pegylated Interferon.