Ch 6, 25, 26 Flashcards
Louis Pasteur
Postulated that rabies was caused by a “living thing” smaller than bacteria
Dimitri Ivanoski
First proposed the term “virus” - poison
Ivanoski and Beijerinck
Showed a disease in tobacco was caused by a virus
Viruses
- Noncellular particles with a definite size, shape, and chemical composition
- there is no universal agreement on how and when viruses originated - likely multiple origins
- considered the most abundant microbes on earth
- infect all domains of life
- viruses played a role in the evolution of bacteria, archaea, eukarya
- obligate intracellular parasites
- not alive
- lack enzymes for most metabolic processes
- lack machinery for synthesizing proteins
- does not consist of one or more cells
- rely on host and and can’t do things independently, like replicate, process, or metabolize
Virus size
- ultramicroscopic - less than 0.2 micrometers; require electron microscope
- largest viruses average around 500-1,000 nanometers (mega viruses and panda viruses), which is 20-50x larger than an average virus
Virus Shape
- some viruses have an external covering, an envelope; those lacking an envelope are naked
- all have capsids (protein coats that enclose and protect their nucleic acid; each capsid is made of identical protein subunits called capsomers
- the capsid together with the nucleic acid (DNA or RNA) is the nucleocapsid
*shape is determined by the nucleocapsid
Two structural capsid types
- Helical: continuous helical of capsomers forming a cylindrical nucleocapsid
- Icosahedral: three dimensional, symmetrical polygon, with 20 sides and 12 evenly spaced corners
*complex/irregular: those that “don’t follow the rules”
- regular shapes often lead to aggregate/crystal formation
Helical Capsids
Nucleocapsid Assembly:
- rod-shaped capsomers assemble into hollow discs
- the nucleic acid is inserted into the center of the disc
- elongation of the nucleocapsid progress from both ends, as the nucleic acid is coiled inside
Icosahedral Capsid
Icosahedral: three-dimensional, symmetrical polygon, with 20 sides and 12 evenly spaced coroners
- arrangements of capsomers vary among Icosahedral viruses
- they can also vary in number of capsomers
- during assembly of the virus, the nucleic acid is packed into the center of the icosahedron, forming the nucleocapsid
- they can be enveloped or naked
A) Rotavirus (naked)
B) Herpes simple (enveloped)
Structure of Complex/Irregular Virus
Atypical Viruses
- Poxviruses: lack a typical capsid and are covered by a dense layer of lipoproteins
- Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers
General Structure of Envelope Viruses
- mostly in animal viruses
- acquired when the virus leaves the host cell (source varies)
- exposed proteins on the outside of the envelope], called spikes, are essential for attachment of the virus to the host cell
Functions of capsid/envelope
- protects the nucleic acid when the virus is outside of the host cell
- helps the virus bind to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell
- capsids are “metastable” structures
- disruption of external structures renders particle non-infectious
Viral Genome
- either DNA or RNA
- carries genes necessary to invade host cell and redirect cells activity to make new viruses
- number of genes varies for each type of virus - few to hundreds
DNA Viruses
- usually double stranded but may be single stranded
- circular or linear
RNA Viruses
- usually single stranded, may be double stranded, may be segmented into separate RNA pieces
- ssRNA genomes ready for immediate translation are positive-sense RNA
- ssRNA genomes that must be converted into proper from are negative-sense RNA
Other substances packaged in viruses
Pre-formed enzymes generally required for viral replication
- Polymerases: synthesize DNA or RNA
- Replicases: copy RNA
- Reverse transcriptase: synthesis of DNA from DNA (HIV virus)
*matrix protein enzymes (not found in all viruses)
Virion
Complete Infectious Particle
- consists of covering: capsid & envelope (not found in all viruses)
- consists of central core: nucleic acid molecules (DNA or RNA) & matrix protein enzymes (not found in all viruses)
Virus Classification
Classification based on numerous characteristics
- nucleic acid type
- presence or absence of envelope
- capsid symmetry
- dimension of virion and capsid
Virus Taxonomy and Phylogeny
- lack of information on origin and evolutionary history makes viral classification difficult
- a uniform classification system developed in 1971 by the international committee for taxonomy of viruses (ICTV); most current report 2,00 viruses, 6 orders, 87 families, 19 subfamilies, and 349 genera
Alternative Classification Scheme
David Baltimore (focuses on viral genome and process used to synthesize viral mRNA
- 7 life cycles groups based on:
- double stranded DNA
- single stranded DNA
- double stranded RNA
- single stranded RNA (+ or -)
- retrovirus
Viral Replication
- Adsorption: attachment to the host
- Penetration/Uncoding - entry of genome into the host
A. Get genome into host cell
B. Deliver to specific location in the cell - Synthesis: using the host to make viral proteins and nucleic acids
A. Copy genome
B. Make viral proteins - Assembly/Maturation: assembly of new virons
- Release: various consequences to host cell
Review of Transduction/Bacteriophage Replication
- Adsorption and Penetration: phage is adsorbed to receptor site on bacterial cell wall, penetrates it, and inserts its DNA
- Biosynthesis: the phage DNA directs the cell’s metabolism to produce viral components proteins and copies of phage DNA
- Maturation: heads are packed with DNA
- Release: bacterial cell lyses, releasing completed infective phages
Viral Specificity
- Defined by whether a virus can attach to a cell
- Requires two things
1. A receptor on the host cell
2. A protein on the virus that recognized and attaches to the receptor
*This will define the tropism of a virus
Process of the Penetration/Uncoating
- entry of genome into the host
A. Get genome into host cell
B. Deliver to specific location in the cell (DNA - nucleus) or (RNA - cytosol) - most viruses enter through one of two means
- fusion: (envelope viruses) - viral envelope fuses directly with host membrane by rearrangement of lipids
- endocytosis: (enveloped or naked) - entire virus is engulfed and enclosed in a vacuole or vesicle. Once inside, the virus is uncoated and viral nucleocapsid or nucleic acid is released
Process of synthesis
Using to make viral proteins and nucleic acids
A. Copy Genome
B. Make viral proteins
- varies depending on whether the virus is a DNA or RNA virus
- DNA viruses generally are replicated and assembled in the nucleus - often use host enzymes
- RNA viruses generally are replicated and assembled in the cytoplasm - often use viral enzymes; RdRp = RNA-dependent RNA polymerase - must make or bring with it
- positive-sense RNA contain the message for translation
- negative-sense RNA must be converted into positive-sense message
Process of release
Various consequences to host cell; chronic release (budding or exocytosis)
Or lysis/cell death
Persistent Infections
- cell harbors the virus and is not immediately lysed
- can last weeks or host’s lifetime; several can periodically reactivate
- chronic latent state
- some animal viruses enter the host cell and permanently alter its genetic material, resulting in cancer
- these viruses are termed oncogenic, and their effect on the cell is called transformation
- transformed cells have an increased rate of growth, alterations in chromosomes, and the capacity to divide for indefinite time periods resulting in tumors
- mammalian viruses capable of initiating tumors are called oncoviruses
- papilloma virus - cervical cancer
- Epstein-Barr virus - Burkitt’s lymphoma
Observable changes/damage in virally infected cells
Cytopathic effects: cell damage altering microscopic appearance
- disorientation of individual cells
- gross changes in shape or size
- intracellular changes (inclusion bodies, syncytium)
Cytopathic changes in specific viruses
- smallpox:cells round up; inclusions appear in cytoplasm
- herpes simplex: cells fuse to form multi nucleated syncytia; nuclear inclusions
- adenovirus: clumping of cells; nuclear inclusions
- poliovirus: cell lysis; no inclusions
- renovirus: cell enlargement; vacuoles and inclusions in cytoplasm
- influenza virus: cells round up; no inclusions
- rabies virus: no change in cell shape; cytoplasmic inclusions (Negri bodies)
- measles virus: syncytia form (multinucleate)
Medical importance of viruses
- viruses are the most common cause of acute infections
- several billion viral infections per year
- some viruses have high mortality rates
- possible connection of viruses to chronic afflictions of unknown cause
- viruses are major participants in the earth’s ecosystem
Detection and treatment of animal viral infections
- more difficult than other agents
- consider overall clinical picture
- take appropriate sample
- infect cell culture - look for characteristic Cytopathic effects
- screen for parts of the virus
- screen for immune response to virus (antibodies)
- antiviral drugs can cause serious side effects
Extra take home messages
- viruses are very different from other infectious agents
- to truly understand them, you need a very firm grasp on the basics of DNA structure and replication, RNA transcription, and protein translation process
- the trick with each type is to ask what is the shortest set of cellular events to get from the viral genome inserted into the cell to newly-made virus particles
- events for each group of viruses will come in handy when thinking about how to interrupt these cycles with antiviral drugs
Parvoviruses
- non-enveloped, ssDNA
- primarily transmitted via direct/indirect contact
- small diameter and genome size
- causes distemper in cats, enteric disease in dogs, fatal cardiac infection in puppies
- few cause infections in humans
B19 cause of erythema infectiosum (fifth disease); rash of childhood - children may have fever and rash on cheeks (-slap-face-rash)
- severe fatal anemia can result if pregnant woman transmits virus to fetus (low but know risk)
Human Papillomavirus
Papilloma: squamous epithelial growth, wart, or verruca
- cause by 100 different strains of HPV
- transmissible through direct contact or contaminated fomites; incubation - 2 weeks to more than a year
- most common warts regress over time; they can be removed by direct chemical application of podophyllin and physical removal by cauterization, freezing, or laser surgery
- warts can recur
- warts described by location
- common seed warts: painless, elevated rough growth; on fingers, etc
- plantar warts: deep, painful; on soles of feet
- genital warts: most common STD in US, morphology ranges from tiny, flat, inconspicuous bumps to extensive, branching, cauliflower-like masses
- warts are good at causing uncontrolled growth of cells and avoiding immune recognition
- ten HPV types increase risk for developing reproductive cancer; 2 (HPV16 and HPV 18) account for 70% for metastatic tumors
- early detection through inspection of genitals, women Pap smear to screen for abnormal cervical cells
- three effective HPV vaccines have been approved by the FDA: Ceravix, Gardasil, and Gardasil 9)
Adenoviruses
- non enveloped, dsDNA
30 types associated with human disease (oncogenic only in animals) - infect lymphoid tissue, respiratory and intestinal epithelia and conjunctiva
- spread by respiratory and ocular secretions
- causes colds, pharyngitis, conjunctivitis, keratoconjunctivitis, acute hemorrhagic cystitis
Severe cases with interferon.
Poxviruses
Produce eruptive skin pustules (pocks or pox) that leaves scars
- largest and most complex animal viruses
- have the largest genome of all viruses
- dsDNA
- multiply in cytoplasm in factory areas (break the normal “rules”)
- specificity for cytoplasm of epidermal cells and subcutaneous connective tissues
Smallpox (variola)
First (and ONLY) disease to be eliminated by vaccination - maybe Guinea Worm Disease - others are painfully close (polio, measles, mumps, rubella, tape worm, filariasis)
- exposure through inhalation or skin contact
- infection associated with fever, malaise, prostration, and a rash
- Variola major: highly virulent, caused toxemia, shock, and intravascular coagulation
- Variola minor: less virulent
What enabled smallpox to be eradicated
- Vaccine - effect prophylactically and therapeutically
- Human only host
- Clear mechanism of transmission - isolation to prevent spread
- Obvious signs of disease
Smallpox Vaccination
- the smallpox vaccine uses a single drop of vaccina virus punctured into the skin with a double pronged needle
- routine vaccination ended in 2002 for military and medical personnel
- reintroduced to address mpox outbreak in 2022
Monkeypox (mpox)
MPOX is typically associated with small animals (guinea pigs, not just simians)
- two common clades associated with human infections (West African/Congo Basin)
- 2022 outbreak associated with the less severe West African clade
- not considered an STI however in 2022 primarily associated MSM
Other Pox Virus Diseases
Molluscipoxvirus: much more common Poxviruses. It causes a skin disease called molluscum contagious (think waxy warts)
- distributed throughout the world, with highest incidence occurring in certain Pacific Islands
- in endemic areas, it is primarily an infection of children
- transmittted by direct contact and fomites
- in US, most commonly an STD
- lesions are small, smooth macules in genital area and thighs
- AIDS patients suffer an atypical form which attacks the skin of the face and forms tumor-like growth
Treatment: freezing, electrical cautery, chemical agents (similar to warts)
- many mammalian groups host some poxvirus - cowpox, rabbit pox, mouse pox, elephant pox
- monkeypox in humans - skin pocks, fever, swollen lymph nodes
- cowpox in humans - rare, usually confined to hands; cutaneous sites can be involved
Herpesviruses
- all members show latency and cause recurrent infection; viral DNA forms episome
- clinical complications of latency and recurrent infections become more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses
- common and serious opportunists among AIDS patients
- large enveloped Icosahedral dsDNA
- replicates within nucleus
- most successful virus in humans