Viral Infection and Viral Genomes PDF

Chapter 12.1-12.2 Viral Infection and Viral Genomes Viruses are omnipresent (common), infecting every taxonomic group of organisms including bacterua, eukaryotes and archea. Viruses causes important human diseases like influenza and the common cold. most frequent infections of college students...

Chapter 12.1-12.2 Viral Infection and Viral Genomes Viruses are omnipresent (common), infecting every taxonomic group of organisms including bacterua, eukaryotes and archea. Viruses causes important human diseases like influenza and the common cold. most frequent infections of college students are due to respiratory pathogens such as rhinovirus and Epstein-Barr virus (infectious mononucleosis) and HSV and papillomavirus (sexually transmitted) Also important to the industry: ◦ Bacteriophages are cloning vectors = small genomes in which foreign genes can be instructed and cloned for gene technology ◦ Bacteriophages (lactococcus) production of milk and cheese. They limit population density of host = example is marine algae -> prevent the dominate of any one host species Martinus Beijerink (1851-1931) said that virus is an infectious fluid -> fluid turned out to be infectious particles we now term as visions. When viruses was first discovered they were defined as non-living ◦ They lack metabolisms to use enegry of conduct biosynthesis ◦ Certain viruses can be crystalized like inert chemicals -> tobacco mosaic virus Some scientis have always questioned this because: some bacteria such as clostridium and bacillus species form endospores that can remains viable fro thousands of years ◦ The Endospores exist as inert particles, like virus but can germinate outside any host cell obligate intracellular bacteria (ex. Rickettsia and Chlamydia spp.) metabolize only during growth in host cells. develop inert spore-like forms that survive outside of the host -> they metabolize only during growth in a host cell -> comparable to virus particles (except that they possess ribosomes) The status of “viral life” remains contested, but possession of ribosomes is generally accepted as a key requirement for existence as cells Didier Raoult and colleagues at Aix-Marseille University they describe a new kind of virus that is larger than some bacteria and whose genome is larger than some bacterial genomes. They are mimiruz because it mimics a cell. Amebas phagocytose the virions as they do with bacteria they eat. ◦ Once ingested, the virus takes over the ameba’s cytoplasm, forming virus factories, that resemble a contained living organism ◦ They may be capable of infecting humans - COPD Virus Origins - Theories 1. Virus-first model arguement for this model is that viruses contain many genes found in no livin g cells. non Objections to this model = is that no viruses are ever found to replicate outside host cells. Therefore they always need a host to replicate. definition: proposes that viruses predate or co-evolved alongside cellular life Keyconcept: viruses are ancient, possibly arising before cells 2. Reduction Model (regressive model) definition: suggests viruses are once small parasitic cells that lost complex functions over time (genome reduction) Key concept: Viruses evolved by regressing from free-living organisms. Gradually lost genes necessary for independent life -> obligate intracellular parasites. Example: chlamydias, shows loss of functions that host cells provides. They can further go through reductive evolution, and end up as acellular viruses. 3. Escape Model (progressive model) some viruses, particularly smaller ones - arisen from cell parts that escaped and evolved the ability to infect other cells. The reverse transcriptase of retroviruses such as HIV resembles telomerase, the RNA-containing enzyme that regenerates chromosome ends. Such viruses might have evolved from a telomerase that escaped from a cell. Definition: Proposes that viruses originated from genetic elements that “escape” cells Key concept: viruses evolved from pieces of RNA or DNA that gained the ability to move between cells (ex. Plasmids) Viruses Replicate Host Cells Viral disease arise from replication of viruses within host cells -> which either destroys or weakens the cell They can also induce host responses that weakens the host (over reaction by the immune system). ◦ Some viruse alter host cell genomes to cause cancer Human gut has bacteriophages ◦ Viruses that infects bacteria (phases) (ex. phage T2, which infects Escherichia coli) Viral infection -> Viral replication -> Viral disease Effects: Debilitation and/or death of the host cell Both depend on various host factors, most importantly, the surface receptor molecule In all cases, viruses use a relatively small number of virus-encoded proteins to commandeer the metabolism of their hosts ◦ Antiviral agents are hard to discover ◦ Antiviral agents have severe side effects ◦ Viral genomes mutate fast, even faster than bacteria Mode of action ◦ Most bacteriophages insert their genome into the host cell leaving the empty capsid outside ◦ Within the bacterial cytoplasm the phage genome directs the replication of virus particles (virions) ◦ Virions are released when the host cell lyses ◦ This can be applied in phage therapy = applying bacteriophages to infect and kill antibiotic resistant bacteria. ‣ Example: mycobacterium absceccus was successfully treated with mycophages. ◦ In lab they can be observed as plaque, a clear spot against a lawn of bacterial cells. ‣ Bacteria grows to completely cover the agar except where the bacteria where lyses by phages. ‣ Each plaque arises from single virions or bacteriophage. -> lyse bacterial cells and would leads to infection of adjacent cells ‣ Eventually enough bacterial cells are lyses making the plaque visible under naked eye. ‣ Can be contend as individual infected virions from phage suspension. Measles Virus the virus has an envelope that is derived from the host cell plasma membrane when the virus exits the host cell. When the virus enters a new host -> the envelope fuses with the host plasma membrane -> releasing viral contents to the host cytoplasm After replication process strats again. Spreading virus generates rash of red spots on teh skin, Tobacco Mosaci Virus (TMV) infects a wide range of plant species The proghency virions travels through interconnections to neighbouring cells, Infections results in mottled leaves and stunted growth Cause major agricultural loss Transmission the process of infecting new hosts Different viruses have different modes of transmission Measles is transmitted through droplets of respiratory fluid HIV is transmitted through blood most specifically sexual contact Host Range each species of virus infects a particular group of host species Some viruses only infects a single species (HIV only humans) ◦ Chimpanzee they cannot be infected but they are susceptible to virus that have same ancestry to HIV (SIV) West Nile virus (mosquitos) - broader host range (includes mammal as and birds) Depends on host factors (surface receptor molecules) Tissue Trophism range of tissue types a virus can infect Some have broad, some have narrow Rabies -> nervous tissue, Influenza virus -> infects cells of the respiratory epithelium Depends on host factors (surface receptor molecules) = protein in the surface where virus paticles binds to Virus encoded proteins - to commander the metabolisms of their hosts (profound consequences for medical therapy) Antiviral agents are hard to discover ◦ Few specific parts (compared to bacteria), there are relatively few targets for antibiotic design. Antiviral agents severe side effects ◦ Agents that distrupt viral infections usually harm the host cell as well (viral replications involves so many host cell processes) Viral genomes mutate fast, even faster than bacteria ◦ Small genome of viruses enables them to mutate rapidly within host ◦ no one antiviral agent will work for long, new agents must be found Viruses are capable of binding within host cells in a latent state, where they are inaccessible by the immune system. Viral Genomes key determinant of viral infections is its genome Viruses of the same genotype (such as dsDNA) are more likely to share ancestry with each other, than viruses of different type of genome (RNA) a viral genome: either DNA or RNA ◦ They are more complicated that human genome that are always made up of double stranded DNA ◦ Double or single stranded ◦ The type of genome determines how the virus infects the cell and can influence the course of disease in the patients. ‣ DsDNA viruses (group 1) (herpesviruses and pox viruses) make their own DNA polymerase or uses the hosts’ for genome replication. Their genes can be transcribed directly by a host rna polymerase ‣ SsDNA (group II) (canine parvovirus) Require the host DNA polymerase to generate the complementary DNA strand The dsDNA is then transcribed by host RNA polymerase to make mRNA ‣ DsRNA (group III) Require a viral rna dependent rna polymerase to gernate mRNA by transcribing directly from the rna genome Rotavirus = diarrhea in children Such viruses must packeage a viral rna polymerase with their genome before exiting the host cell ‣ SsRNA (Hepatitis C and SARs) part of group IV They must have positive sense strand (coding strand) that can serve directly as mRNA to be translated to viral proteins They need to make RNA dependent rpolymerase to synthesize a template strand (-) complementary to the (+) strand. The (+) strand for progeny virions is then replicated from the (-) template. ◦ Other RNA viruses (influenza virus) ‣ They package the (-) strand instead of the (+) -> group (V) ‣ They must also package rna dependant rpolymerase, to transcribe (-) to (+) mRNA -> translated by ribosomes ‣ Later rnapolymerase uses (+) rna to synthesize genomic (-) RNA ‣ Then they are packaged ◦ Special case ‣ Retrovirus or RNA reverse transcribing viruses (group VI) ‣ HIV and feline leukaemia virus ‣ Have genomes that consists of (+) strand RNA. ‣ They package reverse transcriptase which transcribes the RNA into a double stranded DNA. The capsid keeps the viral genome intact outside the host ◦ In some species they are further encased by an envelope Envelope formed out of host membranes with embedded viral envelo[pe proteins in some species Capsid and evelope must provide a mechanism of infection for the next host cell ◦ Infection must be one of two types ◦ (1) injection of viral genome into the host cell ◦ (2) uptake into the host cell followed by disassembly or unloading ◦ In either case th original virions loses their identity which is necessary to generate viral progeny. The Baltimore model classification of viral groups is based on: ◦ The genome is composed of RNA or DNA ◦ Single- or double- stranded ◦ If single stranded, whether the strand directly encodes proteins or requires synthesis of a complement that encodes proteins (+sense or -sense respectively) ◦ The type of genome determines how the virus will manufacture progeny virions ‣ Example: RNA virus such as coronavirus or influenza lacks DNA and therefore cannot use cellular DNA polymerase to replicate its genes ‣ Teh virus must encode RNA dependent rna polymerase ◦ Assuming a common host, the different means of mRNA production generate distinct groups of viruses with shared ancestry. 12.2 Viral structure and Diversity The international committee on taxonomy of viruses (ICTV) classifies viruses based on these factors: Capsid form (isosahedral or filamentous) ◦ Icosahedral capsids (fixed size) ‣ Advantage is that it forms a package out of repeating protein units generated by small number of genes ‣ The smaller the viral genomes, the more genome copies cna be synthesized form the host cells limited supply of nucleotides. ‣ Radial symmetry; based on an icosahedron, a polyhedron with 20 identical triangular faces Each triangular faces of the capsid is determined by the same genes encoding the same protein subunit. ‣ Example: herpes simplex virus (HSV) The dsDNA is spooled tightly - under high pressure When capsid enters the cell it is transported to a nuclear pore complex where the pressure is release. The pressure release drives viral DNA into the host nucleus ‣ Poliovirus and papillomavirus have only the plasmids ‣ Herpesviruses have envelope - derived from the hist nuclear or endoplasmic reticulum membrane They have spike proteins that enable to the virus to attach and infect the next host cells ‣ There could be additional proteins in between the capsid and envelope called tegument They are expressed during infection of a host cell and packaged during envelope formation They are released on the cytoplasm, where they help viral replication. ◦ Filamentous ‣ Helical symmetry Capsid monomers forms a helical tube around the genome. It may extend 50 times its width, flexible filament. Vary in length to accommodate different lengths of nucleic acid ◦ Continent for genetic engineering vectors ‣ A helical tube around the genome ‣ Generating a flexible filament ‣ Examples: Ebola virus, tobacco mosaci virus, many bacteriophages Envelope (present or absent) ◦ Derived ] the host membrane ◦ The envelope bristles with virus coded spike proteins that plug the membrane onto the capsid. Host range complex tailed bacteriophages ◦ Head ‣ Icosahedral protein package ‣ Contains genetic material ◦ Tail ‣ Injects genetic material into host cells ◦ Example: bacteriaphage T4 ‣ Icosahedral head containing the pressure-packed DNA, attached to a helical “neck: that channels the nuclei acid into the host cell. ‣ The neck is surrounded by the tail sheath, with six jointed tail fibres that attach the bacteriophage to the host cell surface. ‣ Within the tail, an injector penetrates the host cell envelope, and the release of pressure within the head propels the DNA into the host cytoplasm. Amorphous or complex viruses ◦ No symmetrical form ◦ Poxviruses are large asymmetrical viruses with no symmetrical capsid (Cowpox virus) ‣ Size of vaccina virus approaches the size of some bacteria’ Now is used as a genetic vector to develop vaccines against many animal disease. ◦ Flexible “core wall” ‣ Contains genetic material ‣ Encloses a large number of enzymes and accessory proteins, similar to cells cytoplasm. ‣ The dsDNA genome resembles that of a cell, except that it is stabilized by covalent connection of its two strands at each end. ‣ The core is enclosed loosely by a viral envelope studded with a spike protein ◦ Viral envelope ‣ Studded with spike proteins ◦ Examples: smallpox virus Viral genome size RNA ◦ Small genomes (small as three genes) ◦ Retroviruses ‣ Have small genomes whose synthesis consumes minimal resources thus maximizing the number of virions that can be made from the infected cell. ◦ Avian leukosis virus (ALV) - retro virus that cause lymphoma in chickens ‣ Have three protein encoding genes: gag, pol and env. DNA ◦ Large genomes (approaching cellular genomes) ◦ Herpes simplex virus I ‣ Cause of cold sores and genital herpes ‣ 152 kilo bases and encodes for more than 70 gene products ‣ Includes capsids and envelopes and other proteins ‣ Some include latent proteins that allow for the virus to maintain during its latent state Viroids and Prions Viroids are virus-like infectious agents in which an rna genome is itself the entire infectious particle No protective capsid Most infects plants, fruits and vegetables Circlular, single stranded molecule of RNA that forms base pairs with itself ◦ Circulated form avoids breakdown by rnase enzymes ◦ RNA folds into globnular structures that interacts with host cells Some have catalytic ability same to enzymes: ex. Ribozyme ◦ Example: hepatitis D viral RNA acts like a viroid ribozyme. Prions no nucleic acid at all (no genetic information) Wrongly folded proteins arising out of preexisting cells Mad cow disease Resembles native human proteins Usually brain cell protein Viral Diveristy and Evolution Evolve through natural selection Small genome size and small number of parts enable viruses to mutates tenfold or even a hundredfold faster than their host cells. antigenic drift: rapid mutation ◦ Accumulation of random mutations that lead to curses whose mutant proteins are no longer recognized by host antibodies ◦ New strains of virus ‣ Changes in the genome ‣ Natural selection ◦ No longer recognized by antibodies ‣ Examples: influenza virus continually generates new strains requiring immunization. Viruses evolve at different levels within a host community ◦ Viruses evolve to preferentially infect different species - for example, equine herpesvirus (in horse) versus murine herpesvirus (in mice) within a viral species population. ◦ Different viral strains arise that vary in infectivity and virulence ◦ Closely related viruses may cause disease that are similar (herpes simplex 1 and 2) or different (varicella-zoster versus cytimegalovirus) Within an individual organism ◦ Viruses evolve variants that resists therapeutic agents ◦ Extremely megtable viruses, such as hepatitis C virus and HIV ◦ Evolve a quasi species of diverse strains that infects different tissues within a host. Summary viruses structure and classification Structures ◦ Capsid: protein shell ◦ Genome: DNA or RNA ◦ Envelope: lipid layer? ◦ Enzymes: Reverse transcriptase, integrate Classification ◦ By genome: DNA vs RNA viruses ◦ Baltimore classification: 7 groups based on replication method ◦ By host: animal, plant, bacteria ◦ Tropism: target tissue/cells