Exploring Viruses: An Overview of Their Structures, Replication, and Interactions

1. Chapter 17: Viruses

2. Following the Big Ideas Evolution- – Changes in DNA can lead to phenotypic variation which can be acted upon by natural selection. – Viral and bacterial genomes benefit from their ability to evolve rapidly. • Information and Signaling- – DNA, and in some cases RNA, is the primary source of inheritable information. – A variety of intercellular and intracellular signal transmissions mediate gene expression. – Gene regulation results in differential gene expression, leading to cell specialization. – Biological systems have multiple processes that increase genetic variation. – Viral replication results in genetic variation, and viral infection can introduce genetic variation into the hosts. • Interactions and Systems- – Regulation of gene activity involves intricate interactions with internal and external factors. •

3. Overview: A Borrowed Life • A virus is an infectious particle consisting of little more than genes packaged into a protein coat • Viruses lead “a kind of borrowed life,” existing in a shady area between life-forms and chemicals

4. Viral Structures

5. Microbial Model Systems • Viruses called bacteriophages can infect and set in motion a genetic takeover of bacteria, such as Escherichia coli • E. coli and its viruses are called model systems because of their frequent use by researchers in studies that reveal broad biological principles • Beyond their value as model systems, viruses and bacteria have unique genetic mechanisms that are interesting in their own right

6. A virus has a genome but can reproduce only within a host cell • Bacteria are prokaryotes with cells much smaller and more simply organized than those of eukaryotes • Viruses are smaller and simpler than bacteria • Scientists detected viruses indirectly long before they could see them • The story of how viruses were discovered begins in the late 1800s

7. LE 18-2 Virus Bacterium Animal cell Animal cell nucleus 0.25 µm

8. The Discovery of Viruses: Scientific Inquiry • Tobacco mosaic disease stunts growth of tobacco plants and gives their leaves a mosaic coloration • In the late 1800s, researchers hypothesized that a particle smaller than bacteria caused the disease • In 1935, Wendell Stanley confirmed this hypothesis by crystallizing the infectious particle, now known as tobacco mosaic virus (TMV)

10. Concept 17.1: A virus consists of a nucleic acid surrounded by a protein coat • Even the largest known virus is barely visible under the light microscope • Some viruses can be crystalized • See Bozeman video on viruses: – https://www.youtube.com/watch?v=L8oHs7G_syI

12. Structure of Viruses/ Viral Genome • Viruses are not cells • Viruses are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope • Viral genomes may consist of – Double- or single-stranded DNA – Double- or single-stranded RNA • Depending on its type of nucleic acid, a virus is called a DNA virus or an RNA virus

13. LE 18-4a Capsomere of capsid RNA Capsids and Envelopes ♥ A capsid is the protein shell that encloses the viral genome ♥ A capsid can have various structures ♥ Capsomeres make up capsids! 18 250 mm 20 nm Tobacco mosaic virus

14. LE 18-4b Capsomere DNA Glycoprotein 70–90 nm (diameter) 50 nm Adenoviruses

15. • Some viruses have structures have membranous envelopes that help them infect hosts • These viral envelopes surround the capsids of influenza viruses and many other viruses found in animals • Viral envelopes, which are derived from the host cell’s membrane, contain a combination of viral and host cell molecules

16. LE 18-4c Membranous envelope Capsid RNA Glycoprotein 80–200 nm (diameter) 50 nm Influenza viruses

17. • Bacteriophages, also called phages, are viruses that infect bacteria • They have the most complex capsids found among viruses • Phages have an elongated capsid head that encloses their DNA • A protein tailpiece attaches the phage to the host and injects the phage DNA inside

18. LE 18-4d Head Tail sheath Tail fiber DNA 80 225 nm 50 nm Bacteriophage T4

19. Concept 17.2: Viruses replicate only in host cells • Viruses are obligate intracellular parasites, which means they can reproduce only within a host cell • Each virus has a host range, a limited number of host cells that it can infect, recognized by compatible receptor proteins on the virus and the host • Viruses use enzymes, ribosomes, and small host molecules to synthesize progeny viruses Animation: Simplified Viral Reproductive Cycle

20. LE 18-5 Entry into cell and uncoating of DNA VIRUS DNA Capsid Transcription Replication HOST CELL Viral DNA mRNA Capsid proteins Viral DNA Self-assembly of new virus particles and their exit from cell

21. Viral Envelopes • Many viruses that infect animals have a membranous envelope • Viral glycoproteins on the envelope bind to specific receptor molecules on the surface of a host cell

22. LE 18-8 Capsid Capsid and viral genome enter cell RNA HOST CELL Envelope (with glycoproteins) Viral genome (RNA) Template mRNA Capsid proteins ER Glyco- proteins Copy of genome (RNA) New virus

23. Reproductive Cycles of Phages • Phages are the best understood of all viruses • Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle • See Bozeman video on viral replication: – https://www.youtube.com/watch?v=EqK1CYYQIug&l ist=PLFCE4D99C4124A27A&index=44

24. The Lytic Cycle • The lytic cycle is a phage reproductive cycle that culminates in the death of the host cell • The lytic cycle produces new phages and digests the host’s cell wall, releasing the progeny viruses • A phage that reproduces only by the lytic cycle is called a virulent phage • Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA

25. LE 18-6 Attachment Entry of phage DNA and degradation of host DNA Phage assembly Release Head Tail fibers Tails Synthesis of viral genomes and proteins Assembly

26. The Lysogenic Cycle • The lysogenic cycle replicates the phage genome without destroying the host • The viral DNA molecule is incorporated by genetic recombination into the host cell’s chromosome • This integrated viral DNA is known as a prophage • Every time the host divides, it copies the phage DNA and passes the copies to daughter cells • Phages that use both the lytic and lysogenic cycles are called temperate phages

27. LE 18-7 Phage DNA The phage attaches to a host cell and injects its DNA. Daughter cell with prophage Many cell divisions produce a large population of bacteria infected with the prophage. Phage DNA circularizes Phage Bacterial chromosome Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lytic cycle Lysogenic cycle The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. Certain factors determine whether The cell lyses, releasing phages. Lytic cycle is induced orLysogenic cycle is entered Prophage Phage DNA integrates into the bacterial chromosomes, becoming a prophage. New phage DNA and proteins are synthesized and assembled into phages.

28. Reproductive Cycles of Animal Viruses • Two key variables in classifying viruses that infect animals: – DNA or RNA? – Single-stranded or double-stranded?

29. Class/Family Envelope Examples/Disease I. Double-stranded DNA (dsDNA) Adenovirus No Respiratory diseases, animal tumors Papovavirus No Papillomavirus (warts, cervical cancer): polyomavirus (animal tumors) Herpes simplex I and II (cold sores, genital sores); varicella zoster (shingles, chicken pox); Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma) Smallpox virus, cowpox virus Herpes virus Yes Pox virus Yes

30. Class/Family Envelope Examples/Disease II. Single-stranded DNA (ssDNA) Parvovirus No B19 parvovirus (mild rash) III. Double-stranded RNA (dsRNA) Reovirus No Rotavirus (diarrhea), Colorado tick fever virus

31. Class/Family Envelope Examples/Disease IV. Single-stranded RNA (ssRNA); serves as mRNA Picornavirus No Rhinovirus (common cold); poliovirus, hepatitis A virus, and other enteric (intestinal) viruses Severe acute respiratory syndrome (SARS) Yellow fever virus, West Nile virus, hepatitis C virus Rubella virus, equine encephalitis viruses Coronavirus Yes Flavivirus Yes Togavirus Yes

32. Class/Family Envelope Examples/Disease V. ssRNA; template for mRNA synthesis Ebola virus (hemorrhagic fever) Filovirus Yes Influenza virus Orthomyxovirus Yes Measles virus; mumps virus Paramyxovirus Yes Rabies virus Rhabdovirus Yes VI. ssRNA; template for DNA synthesis HIV (AIDS); RNA tumor viruses (leukemia) Retrovirus Yes

33. RNA as Viral Genetic Material • The broadest variety of RNA genomes is found in viruses that infect animals • RNA viruses lack replication error-checking mechanisms, thus have higher rates of mutation. • Related viruses can combine/recombine information if they infect the same host cell. (flu) • Retroviruses use reverse transcriptase to copy their RNA genome into DNA • Reverse transcriptase is a type of polymerase that transcribes DNA from an RNA template. • HIV is the retrovirus that causes AIDS- rapidly evolves! • Retroviruses have the most complicated reproductive cycles because of the reverse transcriptase stage.

34. LE 18-9 Viral envelope Glycoprotein HIV Capsid RNA (two identical strands) Reverse transcriptase

35. • The viral DNA that is integrated into the host genome is called a provirus • Unlike a prophage, a provirus remains a permanent resident of the host cell • The host’s RNA polymerase transcribes the proviral DNA into RNA molecules • The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell

36. Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. LE 18-10 Proviral genes are transcribed into RNA, the genomes for the next HIV generation and mRNA for the translation into viral proteins. Membrane of white blood cell HIV HOST CELL Reverse transcription Viral RNA Reverse Transcriptase then catalyzes the synthesis of a second DNA strand complementary to the first. RNA-DNA hybrid 0.25 µm HIV entering a cell DNA NUCLEUS Provirus The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelop glycoproteins (made in the ER) Chromosomal DNA RNA genome for the next viral generation The double stranded DNA incorporates as a provirus. mRNA New HIV leaving a cell

37. Evolution of Viruses • Viruses do not fit our definition of living organisms • Since viruses can reproduce only within cells, they probably evolved as bits of cellular nucleic acid • Coevolution exists between virus and host. – Defenses that bacteria have against invasion from phage infection- • Mutant receptor sits no longer recognized by phage proteins • Enzymes that digest foreign DNA evolved (restriction endonucleases- cut up foreign DNA but not host DNA) • As bacteria evolve to resist viral infection, the virus evolves to become pathogenic again. • Lysogenic cycle has evolved to allow bacteria and virus to co-exist for a time before virus becomes pathogenic.

38. Concept 17.3: Viruses are formidable pathogens in animals and plants • Diseases caused by viral infections afflict humans, agricultural crops, and livestock worldwide – Damage or kill cells by releasing hydrolytic enzymes from lysosomes. – Causes infected cells to produce toxins that lead to disease symptoms – Some viruses have toxic components, such as envelope proteins – Many symptoms are due to the body’s attempt at defense.

39. Vaccines and Antiviral Drugs • Vaccines are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen • Vaccines can prevent certain viral illnesses • Antiviral drugs work by interfering with viral nucleic acid synthesis

40. Emerging Viruses • Emerging viruses are those that appear suddenly or suddenly come to the attention of scientists • Emergent diseases are scientific evidence that evolution continues to occur! • HIV is a classic example • The West Nile virus appeared in North America first in 1999 and has now spread to all 48 contiguous states • In 2009 a general outbreak, or epidemic, of a flu-like illness occurred in Mexico and the United States; the virus responsible was named H1N1 • H1N1 spread rapidly, causing a pandemic, or global epidemic • Severe acute respiratory syndrome (SARS) recently appeared in China

41. Figure 17.8 1 m (a) 2009 pandemic H1N1 influenza A virus (b) 2009 pandemic screening

42. LE 18-11 The SARS-causing agent is a coronavirus like this one (colorized TEM), so named for the “corona” of glyco-protein spikes protruding form the envelope. Young ballet students in Hong Kong wear face masks to protect themselves from the virus causing SARS.

43. • Three processes contribute to the emergence of viral diseases – The mutation of existing viruses, which is especially high in RNA viruses – Dissemination of a viral disease from a small, isolated human population, allowing the disease to go unnoticed before it begins to spread – Spread of existing viruses from animal populations; about three-quarters of new human diseases originate this way

44. • Strains of influenza A are given standardized names • The name H1N1 identifies forms of two viral surface proteins, hemagglutinin (H) and neuraminidase (N) • There are numerous types of hemagglutinin and neuraminidase, identified by numbers

45. Viruses and Cancer • Tumor viruses- All tumor viruses transform cells into cancer cells through the integration of viral nucleic acid into host cell DNA. Through a variety of possible mechanisms, cell cycle control is altered Viral Group Ex. /Diseases Cancer Type Retrovirus HTLV-1 Adult leukemia Burkitt’s Lymphoma Herpesvirus Epstein- Barr/infectious mononucleosis Papovavirus Papilloma/human warts Cervical cancer Hepatitis B virus Chronic hepatitis Liver cancer

46. Viral Diseases in Plants • More than 2,000 types of viral diseases of plants are known; these have enormous impacts on the agricultural and horticultural industries • Plant viruses have the same basic structure and mode of replication as animal viruses • Most plant viruses known thus far have an RNA genome and many have a helical capsid • Some symptoms are spots on leaves and fruits, stunted growth, and damaged flowers or roots

47. • Plant viruses spread disease in two major modes: – Horizontal transmission, entering through damaged cell walls (infection is from an outside source- wind) – Herbivores, especially insects, pose a double threat because they can both carry a virus and help it get past the plant’s outer layer of cells – Vertical transmission, inheriting the virus from a parent (virus spreads through plasmodesmata).

49. Connecting the Concepts to the Big Ideas • Evolution- – All living things, and viruses, are subject to genetic mutations or changes in the base sequence of DNA (or RNA in the case of viruses); this is a source of genetic variability that is acted upon by natural selection, allowing for evolutionary change over time. – The phenomena of emergent diseases supports present-day evolution.

50. Connecting the Concepts to the Big Ideas • Interactions and Systems- – Environmental and internal cues may affect gene regulation, which ultimately effects their survival. – Unicellular populations are capable of interactions which affect their efficiency and productivity. • Information and Signaling – Viruses evolve rapidly engaging in lytic and lysogenic cycles as well as transduction. – Retroviruses use reverse transcriptase.