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Viruses Chapter 27 Nature of Viruses All viruses have same basic structure -Nucleic acid core surrounded by capsid Nucleic acid can be DNA or RNA; Circular or linear; Single- or double-stranded Some viruses store specialized enzymes inside their capsids Many animal viruses have an envelope 2 Nature of Viruses 3 Nature of Viruses 4 Nature of Viruses 5 Nature of Viruses 6 Nature of Viruses Viruses are obligate intracellular parasites -Host range = Types of organisms infected -Tissue tropism = Types of cells infected Viruses can remain dormant or latent for years More kinds of viruses exist than organisms 7 Viral Replication Viruses can only reproduce inside cells -Outside, they are metabolically inert virions Virus hijacks the cell’s transcription and translation machineries to express: -Early genes -Middle genes -Late genes End result is assembly and release of viruses 8 Viral Shapes Most viruses come in two simple shapes -Helical -Icosahedral Some viruses are complex -T-even phages = Binal symmetry -Poxviruses = Multilayered capsid Enveloped viruses are polymorphic 9 Viral Shapes 10 Viral Shapes 11 Viruses vary in size, as well as in shape 12 Viral Genomes Vary greatly Most RNA viruses are single-stranded -Replicated in the host cell’s cytoplasm -Retroviruses (HIV) employ reverse transcriptase -Most DNA viruses are double-stranded -Replicated in nucleus of eukaryotic host cell 13 Bacteriophage Are viruses that infect bacteria Viruses have also been found in archaea -Have complex symmetry E. coli-infecting viruses are the best studied -Include the “T” series (T1, T2, etc.) 14 Bacteriophage Exhibit two reproductive cycles -Lytic cycle = Virus kills the host cell -Lysogenic cycle = Virus incorporates into the cell’s genome Lytic phage are called virulent Lysogenic phage are called temperate 15 Bacteriophage Lytic cycle -Adsorption = Viral attachment -Penetration = Viral entry -Synthesis = Viral components are made -Assembly = Components are put together -Release = Viral exit 16 Bacteriophage Lysogenic cycle -Virus integrates into cellular genome as a prophage -Propagates along with host genome -Resulting cell is called a lysogen Phage conversion occurs when the prophage alters the bacterial phenotype -Vibrio cholerae toxin is viral-encoded 17 Induction = Switch from the lysogenic to the lytic cycle 18 Human Immunodeficiency Virus HIV causes acquired immune deficiency syndrome (AIDS) AIDS was first reported in the US in 1981 Some people are resistant to HIV infection -Have mutation in the CCR5 gene -Encodes a receptor for HIV -Also for the smallpox virus 19 Human Immunodeficiency Virus HIV targets CD4+ cells, mainly helper T cells -Without these cells, the body cannot mount an effective immune response -Host may ultimately die from a variety of opportunistic infections Tests for HIV detect anti-HIV antibodies -Not circulating viruses 20 HIV Infection Cycle Attachment = Viral gp120 attaches to CD4 and a co-receptor on host cells Entry = By endocytosis Replication = Reverse transcriptase converts RNA to double-stranded DNA -DNA is incorporated into host genome Assembly = Occurs after a variable period of dormancy Release = New viruses exit by budding 21 22 HIV Infection Cycle During an infection, HIV is constantly replicating and mutating -Initially, gp120 uses CCR5 as a co-receptor -Later, CXCR4 is used -Thus, the mutated virus can infect a broader range of cells 23 Treatments for HIV Research is currently under way in the following five areas: -1. Combination drug therapy -Highly active antiretroviral therapy (HAART) -AZT and protease inhibitors -2. Vaccine therapy -Using a harmless strain of HIV 24 Treatments for HIV Research is currently under way in the following five areas: -3. Blocking receptors -Use chemokines to block CCR5/CXCR4 -4. Disabling receptors -Through mutations in the genes -5. Blocking replication -Use of CAF (CD8+ cell antiviral factor) 25 26 27 28 29 Influenza Flu viruses are enveloped and have a segmented RNA genome -Type A = Serious epidemics in humans and other animals -Type B and C = Mild human infections -Subtypes differ in their protein spikes -Hemagglutinin (H) = Aids in viral entry -Neuraminidase (N) = Aids in viral exit 30 Influenza H and N proteins are constantly changing -Thus we have yearly flu shots, and not a single vaccine -Type A viruses are classified into 13 distinct H subtypes and 9 distinct N subtypes 31 Influenza Flu viruses can also undergo genetic recombination when 2 subtypes infect a cell -This creates novel combinations of spikes unrecognizable by human antibodies -Antigenic shifts have caused pandemics -Spanish flu of 1918, A(H1N1) -Asian flu of 1957, A(H2N2) -Hong Kong flu of 1968, A(H3N2) 32 Influenza New strains of flu originate in the Far East -Virus hosts are ducks, chicken and pigs -In 1997, avian influenza A(H5N1) was discovered -“Bird flu” has killed over 100 people -However, it does not appear to spread between humans 33 Emerging Viruses Are viruses that extend their host range -Considerable threats in the aviation age Hantavirus -Causes deadly pneumonia -Natural host is deer mice Ebola virus -Causes severe hemorrhagic fever -Host is unknown 34 Emerging Viruses SARS -Severe acute respiratory syndrome -Caused by a coronavirus -Host is civets -RNA genome contains six main genes -SARS vaccines currently being developed 35 Viruses and Cancer Viruses may contribute to about 15% of all human cancers Viruses can cause cancer by altering the growth properties of human cells -1. Triggering expression of oncogenes -2. Disrupting tumor-suppressor genes In June 2006, the FDA approved the use of a new HPV vaccine to prevent cervical cancer 36 Prions “Proteinaceous infectious particles” Cause transmissible spongiform encephalopathies (TSEs) -Mad cow disease -Scrapie in sheep -Creutzfeldt-Jacob disease in humans Animals have normal prion proteins (PrPc) -Misfolded proteins (PrPsc) cause disease 37 38 Viroids Tiny naked molecules of circular RNA Cause diseases in plants -Coconuts It is unclear how they cause disease 39