Virology 4 Flashcards
What is the only DNA virus that does not use the nucleus as the site of replication?
Pox viruses
Baltimore classification of B19 virus?
Group 2: Single stranded DNA
What family does B19 belong to?
Paroviridae
What are paroviruses?
-smallest, simple eukaryotic viruses
-Discovered in the 1960’s.
-Human Parvovirus infections (B19 virus) were only recognized in the 1980’s.
-Since then 50 other parvoviruses have been identified.
Paroviruses can be divided into two groups:
- Defective viruses which are dependent on helper virus for replication
- Autonomous, replication-competent viruses.
2 subfamilies of Parvovirdae
-Parvovirinae (vertebrate hosts)
-Densovirinae (arthropod/inverterbate hosts)
*Both groups contain 3 genuses each
Subfamily: Parvovirinae
-Parvovirus e.g mice minute virus
-Erythrovirus e.g B19 virus
-Dependovirus e.g Adeno-associated virus 2
Subfamily: Densovirinae
-Densovirus e.g Junonio coenia densovirus
-Iteravirus e.g Bombyx mori densovirus
-Contravirus e.g Aedes aegypti denosovirus
What is fifth disease?
-A mild rash illness caused by B19 virus
-Also known as erythema infectiosum
-Illness occurs 4-14 days after infection
Symptoms of fifths disease:
-fever
-runny nose
-headache
-rash known as ‘slapped cheek’ rash
-pain and swollen joint (polyarthropathy syndrome)
How is B19 transmitted?
Through cough or sneeze
-Person is contagious when it just feels like a cold and before rash and joint swelling. Once the rash appears they are no longer contagious.
Tropism of B19:
-Human erythroid progenitor cell
-Foetal liver cells
Structure of B19 virus:
-Icosahedral capsid
-Non-enveloped
-ssDNA (linear) non segmented
-25nm
-consists only of protein (50%) and DNA (50%)
Characteristics of capsid:
-2 capsid proteins (VP1, VP2)
-VP1 takes up 5% of the capsid and VP2 takes up 95%
-60 capsomers
-The capsid confers considerable stability on the virions which are resistant to inactivation by pH, solvents or high temperatures (1h @ 50 ° C).
B19 Genome organization:
-Simple organization
-Linear single stranded non segmented DNA genome
-Has structural and structural proteins (VP1,VP2) in between terminal repeats (hairpins).
-VP1 and VP2 are identical except VP1 has a VP1U region (which consists of 229 extra amino acids and is necessary for viral entry)
Disadvantages of studying B19 genome expression:
-Difficult to grow in culture (erythrocyte progenitor cells are needed)
-Poorly understood
-Little known of its biology
B19V replication cycle:
- Virus binds to receptor and enters the cell
- Viral DNA translocates to nucleus
- NS and CAP protein are expressed
- Viral DNA is replicated
- Capsid is assembled
- Cell is lysed and new viruses are released.
(*look at slide 16 for diagram)
B19 infection causes what:
-Loss of red blood cells due to infection of reticulocytes.
-In ~80% patients, there is also arthralgia (temporary arthritis)
-B19 infection in pregnancy can cause miscarriage
-Hydrops fetalis (a condition in which large amounts of fluid build up in a baby’s tissues and organs, causing extensive swelling)
-Aplastic crisis (Reticulocytopenia)
Treatment for B19 infection:
-No vaccine but can be treated with intravenous immunoglobulin therapy (IVIG)
Baltimore Classification for Herpes:
Group 1: single stranded DNA
What family does herpes belong to?
Herpesviridae
3 subfamilies of herpesviridae:
-Alpha herpesviruses
-Beta herpesviruses
-Gamma herpesviruses
Alpha herpesviruses:
(HHV-1) (Herpes simplex also known as cold sores)
-HHV-2 (genital herpes);
-HHV3 (Varicella)/Herpes zoster virus (Chickenpox/shingles)
*Side not HHV means human herpes virus
Beta herpesviruses:
-HHV5 (Human Cytomegalovirus)
Gamma herpesviruses:
-HHV4 (Epstein Barr Virus)
What is latency?
It is a quiescent state of viral infection with minimal effect on cell function
Structure of HHV1 (Herpes Simplex)
-Complex and large (200nm)
-Lipid envelope (10 proteins, gB, gN)
-Tegument (15 proteins)
-Icosahedral nucleocapsid
-Linear ds DNA genome
-Nonlytic (budding)
-gB binds to extracellular matrix proteins
Tropism of HHV1:
Pantropic but sometimes described as neurotropic
What is a tegument?
A mixture of 15 enzymes but has no metabolic acitivity
HHV1 Genome organization:
-Linear double stranded DNA genome
-126kb unique long (Ul) region containing 56 genes
-26kb unique short (Us) region containing 12 genes
-Flanked by terminal repeats and internal intererval repeats
-84 opening reading frames
-3 ori
HHV replication cycle step 1:
- Virus (gB) binds to extracellular matrix
HHV replication cycle step 2:
2.Tegument proteins corrupt cell function and the Viral core (capsid) goes to nucleus.
HHV replication cycle step 3:
- DNA circularizes and transcribes Immediate Early (IE) & Early (E) mRNAs
HHV replication cycle step 4:
- IE & E proteins induce viral DNA replication
HHV replication cycle step 5:
- mRNA for late proteins are produced. Late proteins transported back to nucleus for capsid assembly
HHV replication cycle step 6:
- Loaded Capsids bud into the Golgi/RER
HHV replication cycle step 7:
- Virus matures in an endocytic vesicle
HHV replication cycle step 8:
- Mature virus released from cell
Primary HHV-1 infection:
Is usually Inapparent but some symptoms include:
-Mouth ulcers (Mucosal)
-whitlow (skin), or rare more serious forms
How can HHV-1 remain persistent:
If it is not cleared by the immune system:
-After 1degree infection in buccal mucosa, the infection travels via nerve cells to trigeminal ganglion where it remains latent.
-In some people it reactivates
Reactivated HHV-1 infection:
-Cold sores
-Uveitis/keratitis (rare)
How does HHV-1 become latent:
- Virus (gb) binds to extracellular matrix
- Tegument proteins corrupt cell function, viral core goes to nucleus
- DNA circularizes and transcribes LAT mRNA and a small number of LAT proteins.
How do Latent neurons become permissive (how does the infection reactivate)
A “stress signal” caused by UV rays, other infections or stress
Why are neurons more favorable for HHV1 to establish latency on:
-Neurons do not divide, which allows the viral genome to avoid complete replication.
What is Virion Host shutoff (vhs) protein and where is it located?
-A late protein that switches off host protein synthesis and degrades host mRNA
-Located in the tegument and is encoded by UL41 gene
Joint function of vhs and ICP47 (immediate early gene)
Prevents MHC class I expression on host cells
