Retroviruses Flashcards
What are retroviruses and why are they particularly interesting?
Retroviruses are important human and animal pathogens and are particularly interesting because of their unusual replication cycle.
Retrovirus are enveloped viruses with a single stranded RNA genome.
What do retroviruses package and why?
Retroviruses package reverse transcriptase enzyme in the particle to copy their RNA genome into double stranded DNA.
Retroviruses also package an integrase enzyme and integrate their DNA into the host cell’s DNA.
This allows the retroviral genome to be transmitted to both daughter cells when the infected cell divides.
When does the host cell RNA polymerase transcribe the virus’ genome?
During its replication cycle (and also produces the genome for the new virus particles).
Give an example of a retrovirus that belongs tothe genera of Lentiviruses?
Human Immunodeficiency Virus (HIV)
Where did HIV originate?

HIV is very similar to a virus called SIV (simian immunodeficiency virus), which is found in monkeys.
SIV likely jumped species to humans in the late 19th or early 20th century.
HIV-1 evolved from a SIV that infected chimpanzees whereas HIV-2 evolved from a SIV that infected sooty mangabeys.
How many types of HIV are there?

There are two major types of HIV, namely HIV-1 and HIV-2.
HIV-1 and HIV-2 are genetically distinct, sharing only a 55% sequence identity.
What are the subtypes of HIV-1 and HIV-2?
Each type of HIV can be further broken down into groups, which themselves can be subdivided into clades (i.e., subtypes).
HIV-1 comprises groups M (main), O (outlier), and N (non-M or O).
There are two main HIV-2 subtypes, A and B.
What is the most common form of HIV?
HIV-1 is the most common type of HIV; 95% of people living with HIV globally have HIV-1.
Describe the structure of HIV.
HIV is an enveloped virus that has a complex structure.
The genome is in the form of a nucleocapsid, and is packaged within the virus capsid along with reverse transcriptase and integrase.
The matrix protein lies between the capsid and the viral envelope.
Two viral envelope proteins are present; SU (gp120) binds to the CD4 receptor and a chemokine receptor, and TM (gp41) is the fusion peptide that results in the viral envelope fusing with the cell’s plasma membrane, thus releasing the capsid into the cell’s cytoplasm.

What does the HIV virus envelope contain?
The virus envelope contains a trans-membrane glycoprotein (TM, gp41) that is joined to a second virus glycoprotein (SU, gp120) by a di-sulphide bond.

What part of HIV binds to the host cell protein CD4?
The gp120 binds to the host cell protein CD4 and the gp41 is the fusion protein.
What lines the inner surface of the envelope in HIV?
The matrix (MA, p17) protein

What is inside the HIV envelope?
A conical capsid made from the virus protein p24 (CA).

What does the HIV capsid contain?
Two (+) sense RNA molecules that are covered with nucleocapsid (NC, p7) proteins, and the enzymes involved in the early stages of genome replication, reverse transcriptase (RT) and integrase (IN).
Protease proteins can be found inside and outside of the capsid.
Vpr is a regulatory protein.

The genome of HIV has several features that are common to retroviruses and distinct from other RNA viruses.
What are they?
The genome is diploid: it consists of two, usually identical molecules of single-stranded RNA.
Both RNA strands are (+) sense with a 5’ cap and a 3’ polyA tail, but it does not serve as a mRNA immediately upon entry into the host cell cytoplasm.
The genome is associated with a specific tRNA (derived from the host cell) that is used to prime the synthesis of DNA.
Finally, the genome is synthesized and processed by the host cell mRNA “handling machinery” after the virus has integrated its DNA into the host cell chromosome in the previous round of infection

What are the three major genes that HIV has that are common to all retroviruses?
HIV has three major genes (gag, pol and env) that are common to all retroviruses.

What are the genes that HIV has that code for regulatory and accessory proteins?
HIV has six genes that code for regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) proteins.

What is the gene order in all Retroviruses?
The gene order in all Retroviruses is invariant:
5’ – gag– pol– env– 3’.

Describe the HIV genome.
The genome of a HIV consists of two identical (+) RNA molecules.
Although these resemble mRNA molecules, they are not translated by the ribosomes when the virus infects the cell.
The gene order for all retroviruses is 5’ – gag – pol – env – 3’.
The gag gene encodes structural proteins, the pol gene encodes the enzymes needed in genome replication, and the env gene encodes the envelope proteins needed to bind to host cells.
Note: This diagram is showing the DNA structure after the process of reverse transcription

What does the gag gene encode?
The gag gene encodes the Gag polyprotein, that when cleaved yields the CA, MA and NC proteins.
What does the pol gene encode?
The pol gene encodes the Pol portion of the Gag/Pol polyprotein, that when cleaved yields the enzymes PR, RT and IN.
The PR becomes activated after the assembly of the virus particle and cleaves the Gag and Gag/Pol polyproteins at specific sites.
What does the env gene encode?
The env gene encodes the Env polyprotein, that when cleaved yields the gp120 and gp41 proteins.
Reverse transcriptase is an enzyme unique to Retroviruses and has at least three different enzymatic activities.
What are they?
- an RNA dependent DNA polymerase,
- RNase (an enzyme to degrade RNA), and
- a DNA dependent DNA polymerase.
What are the key points in the process of reverse transcription of the RNA genome in HIV?
- RT uses a tRNA as a primer to synthesize a DNA copy of the RNA genome. This creates a DNA:RNA hybrid molecule,
- RNase H removes most of the RNA strand (this particular form of RNase can digest the RNA in hybrid molecules),
- the remaining RNA is then used as a primer for synthesis of the complementary strand of DNA,
- the RNA has been copied to yield a double stranded DNA molecule.






















