Retroviruses-Introduction

 

Introduction:

 

Retroviruses are a class of their own kind of RNA viruses:

1.     Contain two single strand genomes with plus sense.

2.     It is unique in the sense, though these RNAs can act as mRNAs, they are not translated after infection; in this regard none of the other RNA viruses exhibit this feature.

3.     They are unique in the sense they are not translated, but copied into cDNA.

4.     Then they are integrated into host genome as proviruses.  

5.     They are unique viruses, which carry their own RNA-dependent DNA polymerase.

6.     The size of the cDNA integrated is slightly larger than the original size of genomic RNA.

7.     Its genome cannot replicate in cytoplasm RNA to RNA form,

8.     It is the integrated viral genome (cDNA) generates full length viral RNAs, viral proteins and they in turn produce viral particles. 

9.     There is a large time laps between the infection and the manifestation of symptoms, so it has a delayed effect, so the name retro viruses. 

10.  It is now well known that many or most of them cause one or the other forms of cancer diseases.  Discovery of these viruses dates back to 1911, when Peyton Rous found out the cause for cancer in chicks and monkeys in South Africa.

 

 

                    Historical Review

 

1904:  Alderman and Bang looked for infectious bacteria in chicks with leukemia, and succeeded in transferring the infected tissue to others, which developed the disease.

1905: Paul Ehrlich demonstrated immune surveillance where tumors formed in living tissues are eliminated by immune system.

1908: Paul Ellerman and Bang succeeded in transferring the disease from one tissue to other (searching for leukemia causing agent)

1910: Francis Rous Peyton (1879-1970) discovered infectious agent. (RSV) responsible for causing cancer (1966 got Nobel Prize).

1960: Howard Temin demonstrated the retroviruses contained RNA as genome and they are replicated by Temin’s enzyme, colloquially called Reverse transcriptase (RT); it is actually RNA dependent DNA polymerase inhibited by Actinomycin D.

1951: Gross observed the cancer can be transmitted vertically, that is germ line transmission.

1969: Huebner and Todaro showed and hypothesized that transmission of oncogenic characters is due to transmission of genetic material.

1981: Human T-cell leukemia virus was discovered.

1983: HIV was discovered; controversy built up between French and USA scientists, about who discovered the HIV virus first?

 

Classification of Retroviruses:

 

 

 

Viral Types:

 

 

Classification of Retroviruses:

 

"http://en.wikipedia.org/wiki/Rous_sarcoma_virus" Categories: Retroviruses.

 

 

 

 

 

Morphological features:

 

 

HIV infects one particular type of immune system cell. This cell is called the CD4+T cell, also know as a T-helper cell (see How the Immune System Works for details on T cells). Once infected, the T-helper cell turns into a HIV-replicating cell. T-helper cells play a vital role in the body's immune response. There are typically 1 million T-cells per one milliliter of blood. HIV will slowly reduce the number of T-cells until the person develops AIDS.

 

http://science.howstuffworks.com/

To understand how HIV infects the body, let's first look at the virus's basic structure. Here are the basic parts of the HIV virus:

 

Viral envelope - This is the outer coat of the virus. It is composed of two layers of fatty molecules, called lipids. Embedded in the viral envelope are proteins from the host cell. There are also about 72 copies of Env protein, which protrudes from the envelope surface. Env consists of a cap made of three or four molecules called glycoprotein (gp) 120, and a stem consisting of three to four gp41 molecules.

 

p17 protein - The HIV matrix protein that lies between the envelope and core

 

Viral core - Inside the envelope is the core, which contains 2,000 copies of the viral protein, p24. These proteins surround two single strands of HIV RNA, each containing a copy of the virus's nine genes. Three of these genes -- gag, pol and env -- contain information needed to make structural proteins for new virions.

 

HIV is a  retrovirus, which means it has genes composed of ribonucleic acid (RNA) molecules. Like all viruses, HIV replicates inside host cells. It's considered a retrovirus because it uses an enzyme, reverse transcriptase, to convert RNA into DNA. http://science.howstuffworks.com/

 

 

 

HTLV 1

T cell leukemia virion (deltaretrovirus) Enveloped. Spherical to pleomorphic, about 80-100 nm in diameter. ; http://viralzone.expasy.org

 

HTLV- Genome organization with GAG, POL, ENV, P12, p13.30, Tax and Rex with LTR on either side; http://bioscience.org/

 

Genomes of HIV1 and 2 Genomes:

 

OMFG! The HIV genome contains overlapping/alternate splicing! Look at all those overlapping genes!! HOW DOES HIV DO IT???? How does it KNOW how to splice????  The difference lies in the presence and absence of VPU and VPX, otherwise the genomic contents is same in both. http://www.mcld.co.uk/

 

 

 

Fifteen Retroviruses: ALV, MLV, MMTV, MPMV, MTLV, HIV, HFV, WDSV, RSV, MC29, Ha-MSV, Mo MSV, Ab-MLV (Ab3lson MLV), SSV.

 

 

 Full-length intersubtype recombinant HIV-1 sequences. The color code indicates the subtype origin of different segments of the genomes; regions in white are sequences whose origin has not been determined. The LTRs are hatched because they have not been analysed in detail.;RNA genomes of different retroviruses: Avian Leukemia virus (~7.3kb), Melony leukemia virus (~8.3kb), Mouse mammary tumor virus (~8.6), Human T cell leukemia virus (~8.5kb), Human immune deficiency virus (~9.749kb), and Human spuma R. virus  (~11.2kb). David L. Robertson,¹ Feng Gao,² Beatrice H. Hahn ² and Paul M. Sharp^3; http://www.hiv.lanl.gov/

 

 

 

 

 

 

Tumor generic RNA  viruses and their Carcinogenic Genes:

 

 

 

A List of Oncogenes, Gene product, Source and Disease:

 

According to Sanger’s institute information there are 125-135 cancer causing genes; note- not all of them are carried by retroviruses.

 

 

 

 

A list of few Cellular Oncogenes:

(Sanger’s lab lists about 125-135 cancer genes).