03/09c Retroviruses I Flashcards
How do you determine if a retrovirus is involved in a chronic condition or disease? Name nine criteria
1) Strength of association
2) Consistency of association
3) Specificity of association - is the disease unique to exposure
4) Temporality - does disease follow exposure?
5) Biological gradient - does increased dose lead to more rapid onset or severe symptoms
6) Plausibility
7) Coherence
8) Experiment
9) Analogy - comparable association with a related virus or disease
What is a retrovirus?
A virus that has an RNA genome and uses a viral reverse transcriptase (RT) enzyme to produce a complimentary DNA (cDNA) copy
What were the first pathogenic human retroviruses that was discovered?
Human T Cell Leukemia Virus (HTLV) 1 & 2
Human Immunodeficiency Virus (HIV)
How do retroviruses differ from other single-stranded RNA viruses?
Retroviruses have an enzyme in the viral particle - reverse transcriptase
Their ssRNA genome is a template for cDNA
What types of diseases are associated with retroviruses?
Rapid and long-latency malignancies (leukemia)
Wasting diseases
Neurological diseases
Immunodeficiency syndromes (AIDS)
What organisms do retroviruses infect?
Humans Cats Mice Chickens Horses, goats, cows
What is similar between ALL retroviruses?
Virion structure - physical properties
Genome organization
Replication mode
How are retroviruses classified?
Based on sequence homology
What is the basic genomic structure of a retrovirus?
Genome is a dimer of linear, (+) sense, single-stranded RNA
Each virus has Gag (structural proteins), Pol (replication enzymes), and Env (envelope) genes
Different retroviruses have other unique genes, some of which may be regulatory
What is encoded by the Gag gene?
Matrix protein (membrane-associated) Capsid and nucleocapsid proteins
What is encoded by the Pol gene?
Protease - cleaves proteins during maturation
Reverse transcriptase
Integrase - for integration into host genome
What is encoded by the Env gene?
Viral attachment factors - surface glycoprotein and transmembrane protein
What are endogenous retroviruses?
Ancient retroviruses that integrated into our genomes a long time ago
Have been found to be associated with certain diseases (cancer, neurological diseases, autoimmune disorders) but none have been found to be causitive
What disease is caused by HTLV-1 infection?
Adult T cell leukemia and tropical spastic paraparesis - only in about 5% of cases
Some reports of coinfection with HIV (10-15% of cases)
Most cases of infection with HTLV-1 are asymptomatic
What human retroviruses do not cause disease?
HTLV-2 and HTLV-5
Have been shown to be ASSOCIATED with certain leukemias, but not causative
What are HTLV-3 and HTLV-4?
Emerging human retroviruses
Not yet shown to cause human diseases
No known human-to-human transmission of either virus
What are two genes that are unique to HTLV?
rex - regulates unspliced Gag mRNA inside the cell
tax - regulatory gene involved in transcription of the genome
How does the accessory gene tax lead to the particular pathology of HTLV?
Tax stimulates production of IL-2 receptor expression
IL-2 receptor cascade leads to abnormal T cell proliferation, which predisposes the host to T cell leukemia
How does HTLV gain access to the host cell?
Hijacks GLUT-1 (ubiquitous glucose transporter) and uses it for attachment
Where is the highest prevalence of HTLV?
Southwest Japan
Caribbean
How is HTLV transmitted? List three ways
Transfusion of blood from an infected donor (before 1989)
Sexual contact with a seropositive partner for several years
Breast milk from a seropositive mother
How is HTLV diagnosed?
ELISA
PCR
What are the clinical manifestations of HTLV infection?
Adult T cell leukemia
Tropical spastic paraparesis - inflammation of the eye, joints, lung, muscle, and skin
How is HTLV infection prevented?
Screening of blood products
Education to prevent unprotected sexual contact or sharing of needles
How is HTLV infection treated?
Glucocorticoids for tropic spastic paraparesis
Chemotherapy for adult T cell leukemia
Antiretroviral drugs?
With what conditions might XMRV be associated?
Chronic fatigue syndrome? Prostate cancer? maybe
It does NOT meet causation requirements!
How does HIV-2 infection differ from HIV-1?
HIV-2 is less common than HIV-1
HIV-2 infections progress much slower than HIV-1 (most infected individuals die of unrelated causes)
How do retroviruses maximize the number of proteins than can produce with a small genome?
Overlapping reading frames
What is the significance of the 5` LTRs in the HIV genome?
Long terminal repeats - contains promoter and enhancer elements that are targets for host and viral regulatory proteins to activate transcription
What is TAR?
Viral regulatory element that is downstream of the 5` LTR
Binds to Tat
What are the two regulatory auxiliary proteins of HIV? What are their functions?
Tat - binds to TAR and stimulates transcription by facilitating initiation and elongation
Rev - regulates viral mRNA production, facilitates export of unspliced or singly spliced RNAs
What are the four accessory auxiliary proteins of HIV? What are their functions?
Nef - can increase or decrease virus replication, help the virus hide from the immune system, and enhances virion infectivity
Vif - increases virion infectivity and is involved in assembly
Vpr - facilitates nuclear entry so the virus can integrate into the host genome
Vpu - involved in virus release
