Viruses Flashcards
Definition of a Virus
Viruses are defined as obligate, intracellular parasites.
Obligate intracellular viruses
Chlamydia and Rickettsiae
DNA viruses families and medically important viruse
Pox Virus (Smallpox virus, molluscum contagiosum virus; DS, LINEAR)
Herpesvirus (Herpes Simple virus, varicella-zoster virus, cytomegalovirus, EBV; DS LINEAR)
Hepadnavirus (Hepatitis B virus; DS, INCOMPLETE CIRCULAR)
Adenovirus (Adenovirus; DS LINEAR)
Papillomavirus (Human papilloma virus, Warts virus; DS, CIRCULAR, SUPERCOILED)
Parvovirus (B19 virus; SS, LINEAR)
Polyamavirus (JC virus, BK virus; DS,CIRCULAR, SUPERCOILED)
RNA viruses families and medically important virus
Orthomyxovirus (Influenze virus)
Reoviris (Rotavirus)
Paramyxovirus (Mumps virus, measles virus, respiratory syncytial virus)
Rhabdovirus (Rabies Virus)
Retrovirus (HIV, human T-cell leukemia virus)
Corona virus
Arenavirus (LCM virus)
Picrornavirus (Polio virus, rhinovirus, hepatitis A virus)
Hepevirus (Hepatitis E virus)
Calcivirus (Norwalk virus)
Flavivirus (Yellow fever virus, dengue virus, West Nile Virus, Hepatitis C virus)
Togavirus (Rubella virus)
Virus structure
Naked Icosohedral
Naked helical
Enveloped icosahedral
Enveloped helica
Physical virus particle. Nucleocapsid alone for some viruses (picornaviruses) or including outer envelope structure for others (retroviruses).
Virion
Regular, shell-like structure composed of aggregated protein subunits which surrounds the viral nucleic acid
Capsid
•morphological unit detected seen under electron microscope
Capsomere
viral nucleic acid enclosed by a capsid protein coat
Nucleocapsid
•lipid bilayer containing viral glycoproteins. The phospholipids in the bylayer are derived from the cell that the virus arose from.
Envelope
*Not all viruses have envelopes some consist of only the nucleocapsid
Methods of inactivating Viruses for Various Purposes
Sterilization (Steam Under Pressure, Dry Heat, Ethylene oxide, y-Irradiation)
Disinfection (Sodium hypochlorite, glutaldehyde, formaldehye, peracetic acid)
Skin disinfection (chlorhexidine, 70% ethanol, iodophores)
Vaccine Production (Formaldehyde, Beta-propiolactone, Propiolactone, Psoralen+UV irradiation, Detergents)
There are about _________ families known. Of these, only _______families contain agents that are human pathogens. This groups is subdivided into _____DNA virus families and ________RNA virus families/
5450; 22; 7; 15
How does a given virus cause disease?
1.Lytic (productive) infection (cell death)
- Productive means that there is a net increase of viral cells produced
- Poliovirus, rabies virus and influenza virus cause disease by this mechanism
2.Non-productive infection (oncogenic conversion)
- Cell is converted from a normal cell to a tumor cell
- Human Herpesvirus -8 , Hepatitis B virus and Epstein-Barr virus cause disease by this mechanism
- Induction of an immunopathological response by the host
* Hepatitis A virus and Hepatitis B virus
Structural properties of viruses
Nucleic acid
- Either DNA or RNA, BUT NEVER BOTH
- dsDNA,ssDNA,dsRNA, ssRNA
- Linear or circular
Proteins
- Capsid proteins, spikes proteins, Envelope proteins, nucleocaspid proteins, RNA-dependent RNA polymerase, reverse polymerase, transcriptional factors
Lipids
- Host membrane that forms envelope
Carbohydrates
- Viral glycoproteins
B19 virus
It is the classic cause of the childhood rash called fifth disease or erythema infectiosum, or “slapped cheek syndrome”.
Parvovirus
The virus is primarily spread by infected respiratory droplets; blood-borne transmission, however, has been reported. The secondary attack risk for exposed household persons is about 50%, and about half of that for classroom contacts
JC virus
Polyomavirus
The virus causes progressive multifocal encephalopathy, by destroying oligodendrocytes, and other diseases only in cases of immunodeficiency
Affects white matter of the brain
FATAL
BK virus
The BK virus rarely causes disease but is typically associated with patients who have had a kidney transplant; many people who are infected with this virus are asymptomatic.
Excreted in urine
HPV
Causes warts
Can lead to cervical cancer
Types
- HPV1 (plantar warts)
- HPV 16 AND 18 (Cervical cancer)
Vaccine: Gardis I
Adenovirus
found to cause a wide range of illnesses, from mild upper and lower respiratory infections in young children (known as the common cold) to life-threatening multi-organ disease in people with a weakened immune system.
Hepatitis B
Affects the liver
Many people have no symptoms during the initial infection. Some develop a rapid onset of sickness with vomiting, yellowish skin, tiredness, dark urine and abdominal pain.
The virus is transmitted by exposure to infectious blood or body fluids.
hepadnavirus family
Primary hepatocarcinoma
Common in HIV/AIDS
Herpes
Herpes cycles between periods of active disease followed by periods without symptoms.The first episode is often more severe and may be associated with fever, muscle pains, swollen lymph nodes and headaches. Over time, episodes of active disease decrease in frequency and severity.
Usually occurs by saliva in the mouth
Types
- HSV-1: Associated with mouth blisters
- HSV-2: Associated with genital infections
Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the ganglion.
Varicella-zoster virus
It causes chickenpox (varicella), a disease most commonly affecting children, teens, and young adults, and herpes zoster (shingles) in adults
Cytomegalovirus
When cells are infected they are enlarged
It may cause infectious mononucleosis
Congenital birth defects (can travel to the placenta)
Can affect heart transplant patients
EBV
Latent infection in B cells
An oncogenic virus
Burkitt’s lymphoma (subsaharan Africa)
Nasopharyngeal carinoma (Asian descent)
Can cause infectious mononucleosis
Smallpox virus
Once inhaled, variola major virus invaded the oropharyngeal (mouth and throat) or the respiratory mucosa, migrated to regional lymph nodes, and began to multiply.
The initial symptoms were similar to other viral diseases such as influenza and the common cold: fever of at least 38.3 °C (101 °F), muscle pain, malaise, headache and prostration.
Molluscum Contagiosum Virus
Often sexually transmitted
Which structure is unique to Herpesvirus?
Tegument
Side effect of smallpox virus vaccination
Encephalopathy
Poxvirus Structure
- The outer surface of the virion is composed of lipid and protein.
- This surrounds the core, which is biconcave (dumbbell-shaped), & two ‘lateral bodies’ whose function is unknown.
- The core is composed of a tightly compressed nucleoprotein & the double-stranded DNA genome is wound around it.
Picornavirus Structure
Rotavirus Structure
Influenza virus Structure
- Influenza virus belongs to the to orthomixovirus group
- Containes helical capsid, enclosed by an envelope.
- Influenza A viruses are negative sense, single-stranded, segmented RNA viruses.
- Viruses are labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase). There are 16 different H antigens (H1 to H16) and nine different N antigens (N1 to N9).
Vesicular Stomatitis Virus Structure
•VSV coat protein (50 aa): alpha helical with 3 distinct domains:
+ charge interacts with nucleic acid, hydrophobic with proteins on either side, negative charge with polar environment
- Subunits are tilted 20o relative to the long axis of the particle.
- VSV Genome: 11,000 nt -ssRNA interacts with the nucleocapsid protein (N) to form a helical structure with P=5 nm. .
Ebola Virus Strucure
- Filamentous Filovirus with single-stranded (-) RNA genome
- The capsid has a helical morphology and is encased inside a membrane envelope.
- VP30- matrix protein; L protein – RNA polymerase
Positive sense
RNA that can be translated to proteins
Only RNA virus family with DS RNA
Reovirus
Poliovirus
Picornavirus
Enterovirus
Poliomyelitis is a disease of the central nervous system
The three serotypes of poliovirus, PV1, PV2, and PV3, each have a slightly different capsid protein.
Ability to more or breath is impaired “iron lung”
Rhinovirus
Picornavirus
Major cause of the common cold
Grow optimally at 25 C- 30 C
Hepatitis A virus
Picornavirus
Liver hepatitis
Spread by the fecal
Only causes acute hepatitis
*Hepatitis B causes both acute and cronic hepatitis
Hepatitis E
Hepevirus
Transmitted by the fecal oral route
Generally only causes acute hepatitis
Mortality genrally low except in pregnant women
Hepatitis E different in that it affects pregnant women
Which type of Hepatitis affects pregnant women?
E
Norovirus (Norwalk virus)
Calicivirus
Viral gastroenteritis
Projectile vomiting
Virus spread by the fecal-oral route
Rotavirus
Reovirus
Rotavirus infects children at a young age but older infants and young children tend to be more symptomatic with diarrhea.
Yellow fever virus
Flavivirus
Symptoms include fever, chills, loss of appetite, nausea, muscle pains particularly in the back, and headaches
In 15% of cases, however, people enter a second, toxic phase of the disease with recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain.
Dengue Virus
Flavivirus
Dengue virus causes dengue fever. Common names for dengue fever include breakbone fever and dandy fever; dengue hemorrhagic fever ([DHF] and dengue shock syndrome (DSS) are the severe forms.
West Nile Virus
Flavivirus
Affects neurons in brain
Hepatitis C
Flavivirus
leads to liver disease and occasionally cirrhosis
Causes both chronic and acute infections
Chronic Hep C can turn into cancer
Type 1: present in African Americans
Treatment
- Harvoni- able to control or eliminated Hep C
- INF (Inteferon Alfa-2B)
Rubella Virus
Togavirus
Really bad in pregnancy
Causes a rash that starts in face and goes to extremities
Congenitial infection and malformaions
Zika virus
Flavivirus
Microencephalopathy
HIV
Retrovirus
Genome is deep diploid RNA (2 copies of the same RNA)
Reverse transcription (transcribed DNA is incorporated into host chromosome
Antigenic drift
a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites.
Occurs as result of point mutation
Influenza virus
Orthomyxovirus
RNA genome with negative sense polarity (cannot function directly as mRNA)
Influenza A
- Influenza type A viruses are categorized into subtypes based on the type of two proteins on the surface of the viral envelope:
- H = hemagglutinin, a protein that causes red blood cells to agglutinate.
- N = neuraminidase, an enzyme that cleaves the glycosidic bonds of the monosaccharide sialic acid (previously called neuraminic acid
Influenza B
- Only causes epidemic
Influenza C
- Asymptomatic infection
Mumps
Paramyxovirus
Nonsegmented negative sense RNA
Paratid glands are swollen
Can causes Sterility in males
Orchitis
Oral meningitis
Measles
Paramyxovirus
Rash starts behind the ears
Lesions in mouth
Koplik’s spots
Rabies
Rhabdovirus
Vesticular stomatis virus
causes inflammation of the brain
symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness
Ebola virus
Filovirus
a viral hemorrhagic fever of humans
a fever, sore throat, muscular pain, and headaches.
Vomiting, diarrhea and rash usually follow, along with decreased function of the liver and kidneys.
virus spreads through direct contact with body fluids
Can cause bleeding from all orafices
DNA enveloped viruses
Herpesviruses
Varicella-zoster virus
Cytomegalovirus
EBV
Human Herpesvirus B
Hepatitis B virus
Smallpox virus
DNA nucleocapsid viruses
Adeovirus
Papillomaviruses
Parovirus B19
RNA enveloped viruses
Influenza
Rubella
Rabies
HIV
Hepatitis C virus
RNA nucleocapsid viruses
Enteroviruses
Cultivation of Viruses
- Primary cell culture (differentiated cells, directly derived from a tissue, limited life span)
- Diploid cell lines ( dedifferentiated, diploid, survive more passages than primary cell lines, but eventually die)
•
•Continuous cell lines (have a mutations that allow the cells to be
passaged many times, heteroploid, mostly originated from a tumor)
Which viruses can detected by culturing green monkey kidney cells?
Enteroviruses
Respiratory viruses
Herpes Simplex Virus
Which viruses can detected by culturing human fibroblasts?
Cytomegalovirus
Varicella-zoster virus
Rhinoviruses
Which viruses can detected by culturing human epithelial cells?
Respiratory Syncytial Virus
Cytopathic Effect (CPE):
•microscopically visible changes in cultured cells; which cells are affected; timing and rate of progression; nature of the morphological changes
Hemadsorption
production by some viruses (I.e. paramyxoviruses: influenza, parainfluenza and mumps) of antigens that can bind erythrocytes of certain species (guinea pig, rat or monkey) - erythrocytes bind to the infected cells
Interference
infection with a virus prevents an infection by a test virus.
___________ is usually a secondary result of changes in the host metabolism caused by viral replication
•CPE
________, __________, or ___________ cells are used to cultivate viruses
•Primary, continuous or transformed
Which cells maintian continous cell lines?
Primary green monkey kidney cells (Vero)
Human fibroblasts (NIH 3T3)
Primary rabbit kidney cells
Human epithelial cells (HEp-2)
Engineered cell lines (HeLa-MAGI, CEM-GFP)
What viruses can grown in the chorioallantoi membrane of a chick egg?
HSV
Poxvirus
Rous sarcoma virus
What viruses can grown in the amniotic sac of a chick egg?
Influenza virus
Mumps virus
What viruses can grown in the yolk sac of a chick egg?
HSV
What viruses can grown in the allantoic of a chick egg?
Influenza
Mumps virus
Newcastle disease virus
Avian adenovirus
Descibed to cause multinucleated cell pneumonia
Measles
How do multinucleated cells form?
- Cell infected with HSV-1 or measles virus
- Cell undergoes antigenic changes on surface
- Cell will recruit uninfected cells to itself
- Virus infects second cell
- Propegation continues
One of first countries to undergo an Ebola outbreak?
Zaire
Negri bodies are often found in cells affected with__________.
Rabies Virus
Lytic infection
Infection in which the host cell is killed
What’s unique about tumor viruses?
They don’t kill the cell and many times become immortalized
Viruses that can cause gastroenteritis
Rotavirus
Astrovirus
Adenovirus
Norovirus
Electron microscopy can be used to directly examine species for which viruses?
Herpesvirus
Poxvirus
Ebola
Electron microscopy
Staining with electron-contrast material, like phopsotungstic acid or uranyl acetate
Evaluation of stool specimens from patients with gastoenteritis
Direct detection of viral particles when viral culture conditions or reagents are not available
Direct examination of speciemens for heerpesvirus, poxvirus, or Ebola
Examination of infected tissue culture
Transmission Electron Microscopy
Beam of electrons is transmitted through an ultra-thin specimen, that fixed and stained with electron-contrast substrates
phosphotungstic acid H3[P(W3O10)4].xH2O
uranyl acetate UO2(CH3COO)2.H2O
An image is formed from the interaction of the electrons with the specimen.
The image is magnified and focused onto an imaging device, such as a fluorescent screen or CCD camera.
CCD- charge couple device
Resolution – 5-7.5 nm (50-75 Å)
Cryo-Electron Microscopy
Rapid freeze and analysis at -1600C
No staining or fixing is needed
The Fourier Transform is used to create 3D structure
Resolution 1-2 nm (10-20 Å)
Viral capsid
Capsids are made up of repeated protein subunits, whcih are held together by noncovalent bonds
Capsids are self-assembled
Mostly helicial or icosahedral symmetry
What are the three basic nucleocapside structures?
Helical
- Rod shaped, varying widths and specific architectures; no theoretical limit to the amount of nucleic acid that can be packaged
Cubic (Isosahedral)
- •Spherical, amount of nucleic acid that can be packaged is limited by the number of capsomers and the size of the viral particle
Irregular
- Without clear symmetry
High symmetry is associated with which type of assembly?
Self assembly. Contain assembly “instructions”
What three cubic (isohedral) symmetries exist?
Tetrahedral- 12 identical subunits
Octahedral- 24 identical subunits
Icosahedral- 60 identical subunits
What type of symmetry leads to isometric (same measurement in three dimensions) particle?
Cubic
Helical viruses
- Organized around a single axis (the “helix axis”)
- Probably evolved along with other helical structures like DNA, a-helix, etc.
- Allow flexibility (bending)
- Helical viruses form a closely related spring like helix instead.
–Note-all animal viruses that are helical are enveloped, unlike many of the phage and plant viruses.
•Most helixes are formed by a single major protein arranged with a constant relationship to each other (amplitude and pitch).
Components of an envelope
Lipids, protein, carbs
Spikes (found only in some) that allow them to attach to the host
What’s the problem with a lipid bilayer as an envelope? How do viruses overcome this challenge?
Such a coating is efficienct because it does not allow the recognition of receptor molecules on the host cell.
It does however protect the virus from desiccation or enzymatic damage
By the synthesis of several classes of proteins which are associated in one of three ways with the envelope
Formation of enveloped viral particles
Uses celleular membranes for assembly
Formation of the particle inside the cell, maturation and release are in many cases a continuous process
The site of assembly varies for different viruses
For which viruses is the site of assembly for enveloped particles the cytoplasmic membranes?
Corona virus
Pox virus
Rhabdovirus
For which viruses is the site of assembly for enveloped particles the nuclear membrane?
Herpesviruses
Three types of electron microscopy
Transmission EM- beam of electrons attempt to travel around and through the specimen that is presented on platform
Cryo EM- Viral suspensions are purified, frozen in liquid nitrogen, and placed in a chamber inside an EM
Scanning EM- Used when attempting to study the surface of viral particles or cells
X-Ray crystallography
Viral particle or protein is purified and crystallized (to make the particle very dense so that it can be examined by an X-ray)
Gives detail down to angstrom level
