VIRUSES Poliovirus – RNA virus, affects humans alone video

what are they? A little more than genes packaged in protein coats

are they living or nonliving? Today scientists agree that they are not alive but exist in this GREY area

“viruses lead a kind of borrowed life” - researches As we saw in the previous chapter about the history of DNA, experiments with viruses provided important evidence that genes are made of nucleic acids. They were also crucial in figuring out the CENTRAL DOGMA mechanism. ALSO … used to manipulate genes and tranfer them from one organism to another

history…

Adolf Mayer 1883 disease of tobacco leaves (mosaic color) could be transferred rubbing diseased leaves onto healthy ones cause invisible under a microscope maybe tiny bacteria?

Dimitri Ivankowsky a decade later filtered out bacteria disease still passed maybe bacteria too small (passed through the filter) or produced toxins?

Martinus Beijerinck infectious agent in the sap could reproduce could NOT be cultivated on nutrient media must be something much smaller than a bacterium (hmmm… what can it be?

Wendell Stanley 1935 crystallized the infectious particle tobacco mosaic virus Crystallized – using X-ray crystallography to get the image of an object (like R. Franklin)

structure of viruses (nucleic acid enclosed in a protein coat, some have a membranous envelope) Is this really it? Is this nothing making us sick???

YEAH!

Helical capsid Icosahedral capsid (20 triangular facets) Influenza virus (8 diff. RNA molecules, glycoprotein spikes) T4 bacteriophage… icosahedral capsid and tail apparatus

and they are not… … good for us

good for us

viral genome We think of genes being made of double stranded DNA… NOT so with viruses!!!!

viruses can posses… double stranded DNA single stranded DNA double stranded RNA single stranded RNA That is quite a variety, isn’t???

usually a single linear or circular molecule of nucleic acid As few as 4 genes or as many as several hundred to thousands… bacteria genome, usually 200 to thousands of genes

capsids and envelopes

capsid Protein shell Protein subunits capsomeres Various shapes

envelopes only some viruses (e.g. influenza) derived from the host cells but also proteins and glycoproteins of viral origin

Bacteriophages (some of the most complex and studied viruses) So how do these guys reproduce???

need a host to reproduce (obligate intracellular parasites) narrow or broad host range Viruses identify the host by a “lock-and-key” fit between viral surface proteins and specific receptor molecules on the outside of cells (these were initially serving the cells but have been modified by viruses as gateways of entry NARROW RANGE: affect single species (e.g. measles – only humans. FURTHERMORE… many viruses affecting multicellular eukaryotes are specific for specific tissues (virus causing a cold or HIV) BROAD RANGE: e.g West Nile virus

in general… virus delivers its genome inside the host cell the host provides nucleotides, and all the components needed to make viral protein (enzymes, tRNA, ribosomes, ATP, etc…) the simplest type of viral reproductive cycle ends with the exit of a large number of viruses Some viruses INJECT their DNA (bacteriophages), some taken up by ENDOCYTOSIS…

simplified viral reproduction

the lytic cycle ends with death of the host cell (lysis) virulent phages virulent phages – only reproduce using the lytic cycle As new viruses emerge from the cell, they can attack more cells… wiping out an entire bacteria population in a short time So why phages have no wipe out all the bacteria??? In fact, they are used to treat some bacterial infections or sprayed on chickens being delivered to consumers to prevent bacterial contamination

how do bacteria fight back? mutations causing unrecognizable receptor are selected for the viral (foreign) DNA is often cut up by restriction enzymes BUT natural selection works for both bacteria and viruses… coevolution

Sometimes phages coexist with their hosts…

the lysogenic cycle does not destroy the host cell viral DNA is incorporated into the host’s DNA (prophage) the viral DNA replicates every time the cell replicates bacteriophages using both modes of reproduction – temperate phages Interesting – one prophage gene codes for a protein that prevents transcription of most of the other prophage genes – enables the viral genome to be silent Well studied example “lambda bacteriophage”

various viral genes are being expressed, changing the phenotype of the host cell (often leading to formation of more harmful bacteria) Besides the gene for transcription preventing protein, other genes are being expressed. e.g. diphtheria, botulism or scarlet fever would not be so harmful to humans without certain prophage genes) e.g. 2 – the difference between the helpful E.coli residing in our intestines and the strain responsible for numerous deadly food poisoning seems to be the presence of a prophage

An environmental signal usually triggers a switchover to the lytic mode This can be a certain chemical or radiation, etc.

reproductive cycles of animal viruses numerous variations, mostly dependent on the type of the viral genome… DNA ? RNA? double stranded? single stranded? Single stranded RNA viruses are further subdivided into 3 classes (IV-VI) according how the RNA genomes functions in the host cell Unlike bacteriophages, many animal viruses have an envelope and RNA genome

viral envelopes used to enter the host cell mostly derived from the host’s plasma membrane Some viruses not an envelope derived from the plasma membrane… e.g herpes viruses – temporarily “wrapped up” in parts of a nuclear membrane, then shed this and replace it in the cytoplasm with a membrane made from the Golgi apparatus In herpes viruses copies of DNA can stay behind in the nuclei of certain neurons as mini chromosomes. They remain latent until some sort of physical or emotional stress triggers the viral production.

RNA as viral genetic material mostly animals infecting viruses class IV – directly used as mRNA class V – RNA serves as a template for mRNA class VI – retroviruses RNA  DNA (reversed transcriptase) e.g. HIV (like other retroviruses – envelope and two molecules of single-stranded RNA) Class V is RNA to RNA – requires a viral enzyme that can carry out the process, there are no such enzymes in most cells Retro – “going back” the genetic information flows in the opposite direction

Retroviruses (class VI) have the most complicated REPRODUCTIVE cycle (HIV) – reverse transcriptase The integrated viral DNA is called provirus …remember prophage? HIV video

evolution of viruses because they depend on cells, most likely evolved after first cells most likely from naked bits of cellular nucleic acids that moved from one cell to another two main candidates: plasmids and transposons two main candidates: plasmids (circular DNA independent of the cell’s genome found in bacteria and yeasts and sometimes transferred between cells) Transposons – DNA segments that can move within a cell’s genome SO PLASMIDS TRANSPOSOMES and VIRUSES have something in common- they are MOBILE GENETIC ELEMENTS

the interesting case of mimivirus described in 1992 at the time the largest known virus (over 400nm in diameter) genome 1.2 M bp 911 protein coding genes it blurs boundaries between viruses and the smallest parasitic cellular organisms This one described in your textbook, However, in 2011 even larger virus Megavirus chilensis (MGVC), about 440nm, 1,120 protein coding genes.. BUT in 2013 Pandoravirus discovered.. THE BIGGEST approaching one micrometer, 1.9 -2.5 M bp, 2556 protein coding genes. ALL THREE infect amoeba

viral diseases in animals Viruses have different ways of killing cells: causing hydrolytic enzymes release from lysosomes Cause infected cells to produce toxins that lead to disease symptoms Some have toxic molecular components (e.g. envelope proteins) How much damage a virus causes partly depends on the ability of cell to reproduce (cold vs polio) Most of the temporary symptoms associated with viral infection results from the body’s own effort to defend itself

vaccine - a harmless variant or derivate of a pathogen that stimulates the IS Currently on the way to eradicate polio and measles effective vaccines also exist against: rubella, mumps, hepatitis B In general… while vaccines can prevent a few viral infections, once the infection occurs, there is not much help, HOWEVER, enzymes that are encoded by viruses provided a target for drugs (acyclovir - inhibits viral polymerase in HSV and thus the DNA synthesis. Various drugs for HIV infection also interfere with DNA synthesis

smallpox – successfully eradicated in 1979 (a vaccination initiative by the WHO) Smallpox: Caused by either variola major or variola minor very narrow host range – only humans… very helpful in its eradicating effort One of the only two viral infections completely eradicated… second is rinderpest (in German: cattle plague) – a viral disease of cattle (2011)

emerging viruses – appear suddenly or are new to medical scientists HIV Ebola virus West Nile virus SARS HIV – SF early 80’s Ebola virus – Central Africa 1976 – cause hemorrhagic fever, vomiting, massive bleeding West Nile – appeared in US in 1999 and spread in all 48 lower states SARS (Severe Acute Respiratory Syndrome) – Southern China, November 2002 – global outbreak within 7 months, infected about 8,000 and killed over 700 (virus identified as a coronavirus, previously NOT known to cause disease in humans)

how do they just show up? (3 reasons) unusually high rate of mutation dissemination from a small isolated human population spread of existing viruses from other animals Point one – errors in replicating of viral RNA are not corrected by proofreading Point two - e. g. HIV infection had gone unnoticed for many years before spread all around the world Point three – ¾ of new human diseases originate this way, animals are natural reservoir of viruses (e.g. SARS virus came from a bat (in China dried feces sold for medicinal purposes… could have been the source)

“Spanish flu” 1918 – 1919 pandemic Influenza virus type A the source: most likely birds Infected about 500M people (killed 50-100M) Types B and C only infect humans and have never caused an epidemic Type A infects many animals… birds, horses, pigs, etc. So the likely scenario is that the virus mutates as it’s passed from one host species to another

Different strain of influenza A are given standardized names… e.g. 

H1N1 (the “Spanish flu” strain) Different strains of influenza A are given names based on the form of two viral surface proteins: hemagglutinin (H) – protein that helps a virus to attach to the host cell (there are 16 of them) and neuraminidase (N) – an enzyme that helps release new viral particles from an infected cell

H5N1 the “avian flu” strain In 1997… 18 people infected in HK, 6 died… the same strain previously only seen in wild birds and killed thousands of chickens the previous year… all domestic birds in HK were killed, which seemed to solve the problem. HOWEVER in 2002 reappeared in SE Asia and in 2007 killed about 160 people

viral diseases in plants more than 200 types $15B estimated annual loss in crop destruction similar basic structure and reproduction cycle as animal viruses horizontal transmission vertical transmission

viroids circular RNA molecules only a few hundreds of nucleotides long do not encode proteins affects plants siRNA (RNA silencing) They cause errors in the regulatory systems that control plant growth, so a typical signs of viroid infection is abnormal development and stunted growth Human hepatitis D virus is very similar to viroids siRNA – small interfering RNA (only about 20-25 base pairs) – double stranded, interferes with expression of certain genes (it’s why it’s significant in viroid because they do not code fro proteins)

Prions (the scariest of all) infectious agent composed only of (misfolded) protein causing TSEs – neurodegenerative disease of the CNS (formation of amyloids) ability to misfold other proteins A long incubation period (5-20 years) Nearly impossible to denature Most known diseases include: BSE (aka mad cow disease) and CJD in humans TSE = transmissible spongiform encelophalopathies BSE = bovine spongiform encelophalopathy CJD = Creutzfeldt Jacob disease