Retroviruses, AIDS, & Tumor Viruses Flashcards
when was AIDS first identified and what acronym was used to describe those infected?
-late 1970s-early 1980s: Homosexual men, heroine addicts, Haitians, and hmeophiliacs (4H risk group) began dying of normally-benign opportunistic infections in the US, defining a new disease
where is the origin of HIV?
appears to have evolved (genetic evidence) from simian virus in Africa (SIV) and spread through the rest of the world due to an increasingly mobile population and aberrant sexual behaviors
eating and harvesting ape meat
describe the retrovirus class
- large and diverse group of viruses
- unique replication cycle
- ubiquitous in vertebrates
- many are benign, cause little to no impact on the host cell or host animal
- others have significant pathogenicity cause disease and cancer
what genus and subfamily do HIV-1 and HIV-2 come from?
- genus: lentivirus
- subfamily: orthoretroviridae
spumaviruses (subfamily of retroviruses) do not cause human disease, however, what kind of structures do they make inside the cell
foamy structures
**what type of viruses are retroviruses?
- retroviridae: 2 subfamilies (othroretroviridae, spumaviridae)
- genome: (+) ssRNA: diploid, identical copies
- virion: enveloped
- proteins:
- reverse transcriptase (RNA->DNA, DNA->DNA)
- integrase
- protease
- *antivirals go after one of these proteins
how were retroviruses once classified?
by nucleocapsid structure & location in the particle
- A type: shell & hollow center, immature particle
- B type: circular NC, eccentric location
- C type: circular NC, central location
- D-type: cylindrical NC, central location (AIDS)
simple retroviruses only encode the ___, ___, ___, and ____ genes
gag, pro, pol, env
what is the replication cycle like for retroviruses?
- attachment: membrane fusion @ cell surf when it inserts itself doesn’t discriminate
- entry
- REVERSE TRANSCRIPTION: ssRNA genome to dsDNA
- INTEGRATION: virus dsDNA into host making provirus
- transcription from provirus
- translation
- assembly
- release by budding
- maturation: protease activity
why is retrovirus replication an exception to the rule?
because makes dsDNA intermediate and uses the nucleus even though it is (+)ssRNA
when does the reverse transcription of retroviruses occur?
initiates once nucleocapsid is in cytoplasm
- need high levels of NTPs present otherwise no transc.
- low NTP levels prevent reverse transcription
where does the reverse transcription of retroviruses occur?
-occurs within a large complex similar to nucleocapsid
can infection progress if reverse transcription does not occur?
no
T/F: reverse transcription in retroviruses is not promiscuous among genome copies
FALSE: “silent” when copies are identical
many different recombinations when different genomes are in the virion
**adds to high mutation=hard to develop vaccine
describe the integration process in retrovirus replication
- must access the nucleus during mitosis b/c requires dividing cells
- importation (mech unknown): can infect nondividing cells
- 3’ end processing of dsDNA
- attack target DNA, nick created
- host repair
is the integration process in retrovirus replication permanent?
yes, no mech to remove it
when is the provirus considered “endogenous” in retroviruses?
if integrated into the germ-line
integration can cause cancer. what are some integration identified oncogenes?
- TFs
- secreted growth factors
- growth factor receptors
- cell signal transduction pathways
many defective viruses are made during replication what are they typically missing?
at least one: gag, pol, or env
however, require complementary infection to make progeny
how is it that most retroviruses are benign?
- not cytopathic
- chronic infections exert small demand on cell and host resources (few percent of cell RNA and protein)
- do cause viremia and elicit an immune response, but host animals live normal lives for many months or years
- viruses are never limited by the host response
*describe slow retroviruses
(eg leukemia viruses)
- effect is like high-level mutagenesis
- eventually results in tumorigenesis
- replication, integration event affects cell growth regulation factor leading to cancer
*describe cytopathic retrovirues
- minority of retroviruses carry cytopathic genes
- cause tissue damage directly
- genes for cell lysis
*describe acute transforming viruses
- induce rapid tumor formation
- carry host genes: mitogenic and antiapoptotic
- often replication defective b/c host gene replaces an essential gene (produce oncogenes–>cancer)
what are the 4 types of human T-cell leukemia (HTLV)
HTLV1-4
what type of virus is HTLV?
deltaretrovirus
what is the HTLV-1 prevalence?
millions of people around the world are infected
how is HTLV transmitted?
person to person:
- mother to child via breastfeeding (endemic areas)
- sharing needles for drug users
- blood transfusions
- sexual transmission (less efficient)
how is HTLV spread within the host?
- highly cell associated/budding out of cell so “hitching a ride”
- primary mode for spread is contact between infected and naive cells
adult T-cell lymphoma/leukemia has a LONG latent period, how long is it?
30-50 years
which T cells does HTLV-1 infect?
memory T cells
what triggers the transcription of provirus in HTLV-1 disease?
antigen activation triggers it
what proteins in HTLV-1 stimulate cell proliferation?
Virus Tax protein and others
in HTLV-1 cells become ________ generating tumors
transformed
with or without protein expression
what is HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)?
- following transfusions
- infected T cells enter the central nervous system
- active astrocytes
- recruit inflamm cells causes further tissue damage
what are the symptoms of HAM/TSP?
- onset typically 3 years after infection
- starts with bladder control issues
- progress to lower back pain, leg weakness, or stiffness in the hips
- men suffer impotence or erectile dysfunction
how can HTLV-1 be prevented?
eliminate breast feeding for HTLV-1 positive mothers
incr. screening for blood products
what treatment is there for HTLV-1?
- ATLL:treat the lymphoma/leukemia with chemotherapy regardless of HTLV infection
- HAM/TSP: corticosteroids, interferon yield temporary relief of symptoms
describe human immunodeficiency virus
- two main types: 1 & 2
- Lentivirus
- Id’ed due to immune deficiency occurring in previously healthy young gay men
- Id’ed in 1984
- specific pops were at risk (4H’s)
is the HIV prevalence worldwide?
yes
where is HIV prevalence highest at?
sub-Saharan Africa
what is the AIDS incidence like?
high rise until 1994 when the AZT(antiviral) was put on the market
what is the primary mode of transmission and the most likely way it is passed between person to person?
sexual transmission and male to male>male to female>female to male
is AIDS latent for a long time?
yes 6mos-25 years
infection begins virus containing _____ or body fluid to a _______ surface or blood
blood, muscosal
which immune cells does HIV target?
memory T cells (CD4+)
when does the initial acute infection of HIV first occur?
2 weeks after infection: mucocutaneous ulceration and weight loss more indicative of HIV infection
what is GALT and what is it a result of?
- gut associated lymphoid tissue
- result of acute HIV infection (reservoir)
does HIV lead to chronic infection
yes, ongoing virus replication & T cell depletion
T/F: opportunistic infections incr. with HIV infection
TRUE
how is HIV prevented?
sexual behavior and protection, blood screening
what is the treatment for HIV?
no vaccine
antiviral treatments:
- nucleoside reverse transcriptase inhibitors (NTI)= azidothymidine (AZT)
- protease inhibitors
- non-nucleoside RT inhibitor
- highly active antiretroviral therapy: combine 3 treatment options
IMPORTANT POINTS OF RETROVIRUSES
- enveloped particle
- diploid (+)ssRNA
- unique replication cycle:
- reverse transcription
- integration into host DNA
- transmitted by sexual contact, blood transfusions, IV drugs
- -signif cause of certain types of cancer
- virus that causes AIDS
