Retroviruses

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Human Endogenous Retroviruses are transmitted via what cell line?

Germ cells

Are Human Endogenous Retroviruses constituitively found in the human genome?

YES. There are thousands in the human genome and make up 8% of the sequence content.

Why don't Human Endogenous Retroviruses constantly cause disease?

Most of the endogenous retroviruses are DEFECTIVE, containing NONSENSE mutations or MAJOR deletions, but some are maintained as active genes.

How are EXOgenous retroviruses different than ENDOgenous retroviruses?

EXOgenous retroviruses are ACQUIRED, whereas ENDOgenous retroviruses get passed by our genes

What are the PRIMARY human retroviral pathogens?

Lentiretroviruses
Deltaretroviruses

What are HIV-1 and HIV-2 related to?

Simian Immunodeficiency Viruses (SIV)

What are the HTLV viruses closely related to?

Primate T-lymphotropic viruses (PTLV)

Are retroviruses enveloped?

YES

How many copies of genetic material do Human Retroviruses have?

Two IDENTICAL copies

Are Human Retroviruses DNA or RNA viruses?

RNA viruses

Are the human retroviruses + or - sense?

+ sense RNA

Is HIV a complex or simple retrovirus?

COMPLEX retrovirus

What do the gag genes encode for?

Core proteins
Structural components

What are examples of pol proteins?

Protease
Polymerase
Integrase

What does env code for?

Envelope glycoprotein

What are LTRs?


What do they allow for?



What do they control?

Long Terminal Repeats

-They are regulatory sequences at each end of a genome that allow for INTEGRATION into host chromosome and help control gene expression


What do they allow for?
INTEGRATION into host chromosome


What do they control?
GENE EXPRESSION

What kind of polymerase does the human retrovirus use for transcription? What is it also known as?

DNA transcription occurs by RNA-dependent DNA polymerase

What is it also known as?
REVERSE TRANSCRIPTASE

What is a PROVIRUS?

A DNA copy of the RNA retrovirus

What happens to the provirus after it has been produced?

It may translocate to the nucleus and integrate into the host cell genome via INTEGRASE

What enzyme is need to integrate the Provirus into the host genome?

INTEGRASE

What part of the human retrovirus allows for the integration of the virus into the host chromosome?

The LTRs (long terminal repeats)

How do Complex retroviral genomes differ from Simple retroviral genomes?


What ones do HTLV have?


What ones does HIV have?

Complex retroviral genomes contain regulatory genes like tat, rev, nif and vif that Simple retroviral genomes do not contain.


What ones do HTLV have?
Tax, Rex (End in X!!)


What ones does HIV have?
Tat, rev

What is an example of a Lentivirus?

HIV

What is an example of a Deltaretrovirus?

HTLV

What is also known as an oncoretrovirus?

Deltaretrovirus

What kind of viruses (Lenti or Delta) cause cellular transformation?

What other disease does this?

Deltaretroviruses



What other disease does this?
Epstein Barr Virus

What retrovirus can lead to cellular transformation and oncogenesis?

HTLV

What is meant by a "cytopathic" effect? What retrovirus does this?

Cytopathic means "destruction of CD4 cells"

What retrovirus does this?
HIV

What clinical feature do HIV and HTLV share in common?

Prolonged asymptomatic period

Where did Leniviruses arise from (what species)?

Primates

What are the clinical manifestations of Lentiviruses in most primates?

NO IMMUNOPATHOLOGY or CLINICAL DISEASE.
*There is an absence of CD4 cell loss, a lack of generalized immune activation, and preservation of lymph node architecture,

What are the reservoirs for Lentiviruses?


Why do they serve as reservoirs?

Primates


Because of persistent VIREMIA

How are animal Lentiviruses the same as those seen in man?


How are they different?

They can have sustained viremia


How are they different?
Animals retain their CD4 lymphocyte renewal capacity

What do the M and O HIV groups stand for?


What group are most viruses in?


What differentiates the groups?

M = Main
O = Outgroup


Most viruses are in Group M


env sequences differ by 30-50% between the groups

What are CLADES?

HIV subtypes that vary geographically, but diverge from a common ancestor

What are almost all HIV strains in the US (group and clade)?

Group M
Clade B

What are circulating recombinant forms (CRFs)?

Where do these occur?

CRFs are different clades that combine gene segments to form HYBRIDS


Where do these occur?
These occur in several regions of the world where more than one HIV clade is circulating

What is important for HIV vaccine design?

Clade diversity

What does tat stand for? What is it for?

Trans-Activator of Transcription

Required for elongation of viral transcripts

What does rev stand for? What is it for?

REgulator of Virion

It Promotes nuclear export of incompletely spliced/unspliced viral RNAs

What does nef stand for? What is it for?

NEgative Factor


It downregulates host cell CD4 and MHC class I expression; INCREASES viral release from cells

What does vif stand for? What is it for?

Viral Infectivity Factor


It enhances infectivity of viral particles

What does vpu stand for? What is it for?

Viral Protein U


It down-regulates host cell CD4 expressionl INCREASES viral release from cells
(SAME AS Negative Factor nef!)

What does vpr stand for? What is it for?

Viral Protein R


It promotes nuclear IMPORT of viral DNA;
It arrests cell cycle at G2

What is tax for?

Elongation of viral RNA transcripts in HTLV

What is rex for?

Nuclear export of viral RNA in HTLV

What is gp120?

What does it help accomplish?

gp120 is a surface glycoprotein in HIV

It helps with HIV ATTACHMENT

What is gp41?


What does it help accomplish?

gp41 is a transmembrane anchor.


It helps with HIV ENTRY

What on the HOST cell is needed for ATTACHMENT and ENTRY of HIV?

CD4 receptors, CXCR4 and CXCR5 chemokine receptors

Where are CD4 receptors found?

T lymphocytes
Follicular dendritic cells
Macrophages

What are the essential steps in HIV replication?

Attachment
Entry
Reverse Transcription
Nuclear Translocation
Integration
Transcription
RNA Processing
Translation
Assembly
Maturation

How is Reverse Transcription able to result in drug resistance?

Reverse TRANSCRIPTASE is error-prone and fails to correct transcription errors. The point mutations that arise can lead to resistance to these drugs:

Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

What HIV regulatory gene products take control over cellular events?

Tat and Rev

How do Tat and Rev work?

They bind to specific HIV RNA regions

What are the membranes and center of Immature HIV Particles like?


What are the membranes and center of MATURE HIV particles like?

Immature Particle: THICKER membrane, Amorphous center


Mature Particle: Thinner membrane, core center

Why is there HIV-2?

It is a Cross-species transmission from the sooty mangabee

Where is HIV-2 primarily found?

West Africa and India

How do the transmission rates of HIV-2 compare to HIV-1?

LOWER transmission rates

What do you need to know about HIV-2?
transmission rates
pathogenic
rate of progression
prevalence
where is it

Lower transmission rates
Less pathogenic
SLOWER rate of progression
Less prevalent
Mostly West Africa

How many groups of HIV-2 are there?

Which ones are primarily found in man?

8 groups


Which ones are primarily found in man?
A and B

What cancers are associated with HTLV?

Human T cell lymphoma
HTLV-1-associated myelopathy
Tropical spastic paraparesis

What cells do HTLV infect?

CD4 cells
CD8 cells
Endothelial cells
Fibroblasts

Where is HTLV endemic?

Caribbean and Japan

What does infection with HTLV lead to?

Cellular TRANSFORMATION

What does tax do?

It activates transcription of viral and cellular genes that facilitate viral expression

What does rex do?

Regulator of EXpression

It stabilizes mRNA for export to the cytoplasm
It favors production of structural proteins and downregulates tax

How is HTLV transmitted?

What are the most common modes of transmission?

It is transmitted via CELL-ASSOCIATED virus

What are the most common modes of transmission?
IV drug use
Contaminated blood products

Can HTLV be transmitted sexually?

YES

Can HTLV be vertically transmitted?

Unlikely

How can infants be transmitted with HTLV?

Infants can ingest infected lymphocytes in breast milk

What are the Late manifestations of HTLV-1?

T-cell Lymphoma
Tropical spastic paraparesis

What does HTLV-2 rarely cause?

Milder HTLV-2 Tropical Spastic Paraparesis

Where was HTLV-3 recently identified?

Cameroon

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