Retroviruses-Introduction

 

Introduction:

 

Retroviruses are a class of its 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 Teminís 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:

 

Genus

Species

Avian type C rtvs

Avian leucosis virus

BLV-HTLV Rtvs

Bovine leukemia virus

Lenti viruses

HIV-1

Mammalian- type B Rtvs

MMTV

Mammalian- type C Rtvs

Murine leukemia virus

Spuma virus Rtvs

Human Spuma virus (HSRV)

Type D viruses Rtvs

Mason-Pfizer monkey virus (MPMV)

 

 

Viral Types:

 

Viral-Type

Features

A-type

Non-enveloped, immature, inside cellular cisternae, 100nm size, have retroviral like genetic material, also called intra cisternal particles found in ER vesicles.† They are noninfectious immature previral particles.† They are seen only inside the cell as endogenous retroviral like genetic elements.

 

B-type

Enveloped MMtrV, 100nm size, they are extra cellular budded off particles, enveloped, and condensed, with acentric core, ex. MMtrV.

 

C-type

RSV, MuMLV, ALV, HTLV-1 and HTLV-2, HIV-1, 100nm size, they have well-organized central core, spikes are barely visible, ex. Mammalian and birdís viruses

D-type

MPMV, 120nm largest, they resemble B-types, spikes are not very prominent, all are Lentiviruses,-HIV1, 2 Visna, FIV,SIV,EIAV

 

E type

Bovine Leukemia

HTLV1

HTLV2

 

Classification of Retroviruses:

 

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

 

 

Virus: Retroviruses

 

 

SsRNA-RT virus/
retroviridae

Alpharetrovirus

Avian Sarcoma Leukosis Virus ∑ Rous sarcoma virus

 

 

Betaretrovirus

Mouse mammary tumor virus  ∑ Jaagsiekte sheep retrovirus

 

 

Gammaretrovirus

Murine leukemia virus ∑ Abelson murine leukemia virus ∑ Feline leukemia virus ∑ Xenotropic murine leukemia virus-related virus

 

 

Deltaretrovirus

Human T-lymphotropic virus (HTLV-1, HTLV-2) ∑ Bovine leukemia virus

 

 

Epsilonretrovirus

Walleye epidermal hyperplasia virus

 

 

Lentivirus

HIV ∑ SIV ∑ FIV ∑ Puma lentivirus ∑ EIA ∑ Bovine immunodeficiency virus ∑ Caprine arthritis encephalitis virus ∑ Visna/Maedi virus

 

 

Spumavirus

SFV ∑ HFV

 

 

Other

Metaviridae ∑ Pseudoviridae

 

 

DsDNA-RT virus

Hepadnaviridae (Hepatitis B virus)

 

 

Other

Endogenous retrovirus

 

 

 

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 genomes: 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. Sharp3; http://www.hiv.lanl.gov/

 

 

 

Acronyms

Expanded name

Year- by author

Size and number

Disease

RSV

Rous sarcoma virus

Peyton- 1911

>10.3kb RNA

Cancer in chick and monkeys

ALV

Avian Myeloblastasis virus

 

7.3kb

Leukemia in birds

ALV

Avian Erythroblastasis virus

 

10kb

Leukemia in birds

MMTV

Mouse mammary tumor virus

 

8.6kb

Mammary tumors in mice and monkeys

MoMuLV

Maloney Murine leukemia virus

 

8.3kb

Mice and cats

HTLV 1

†Human T-cell leukemia virus-1

Robert Gallow-1981

8.5 kb

Transform CD4ĖT-lymphocytes

HTLV-2

BLV-HTLV

Human T-cell transforming virus-2

Robert Gallow

8.5kb

CD4-T cell transformation

MPMV

Mason Pfizer Monkey virus

 

 

 

HIV 1

Human immunodeficiency virus

1983

9.749kb

(9719)

Immune deficiency

HIV 2

HIV-2

1985

9.749kb

Helper T-cells deformed

WDSV

Wally dermal sarcoma virus- Fish,

 

12.3-13kb

 

HFV

Human foamy virus,

 

11.2kb

 

HSRV

Human spuma R.virus

 

11.3kb

 

 

 

 

RNA tumor generic viruses and Their Carcinogenic Genes:

 

Virus

Tumourigenic gene

Function

Simian sarcoma (SSV)

V-cis

Growth factor 38KD,

acts like a PDFG

Avian Erythroblastasis (AEBV)

V-erg

EGF receptor

Rous sarcoma virus (RSV)

V-src

60KD, tyrosine kinase

Maloney murine sarcoma virus (MmuSV)

V-moss

Serine-threonine kinase

MC29 avian Myelocytoma virus MCAMV)

V-myc

Transcriptional factor

Kirsten murine sarcoma virus (KMSV)

V-k ras

G protein transducer

Mouse mammary tumor virus (MMtrV)

Int-1, int-2, int-3

 

 

 

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

According to Sangerís institute information there are 125-135 cancer causing genes;

note- not all of them are carried by retroviruses.

 

Gene

Virus

V.onc origin

Onc protein

Disease

Src, c-src

RSV

Chick

Pp60 src

Sarcoma

V.fps (c-fps)

Fu SV, fujumani sarcoma virus

Chick

P/30 src-fps

Sarcoma

 

Prc II-avian sarcoma (asv)

Chick

P 105 gag-fps

Sarcoma

Fes

Synder theilin feline sarcoma V

Cat

P 85 gag-fes

Sarcoma

 

Gardner Aronstein fe-Sv

Cat

P 110-gag-fes

Sarcoma

Yes

Y73-asv

Chick

P 90 gag-yes

Sarcoma

Fgr

Gardner-raheed-fesv

Cat

P70gag-actin-fgr

Sarcoma

Ros

UR2-Asv

Chick

P 68 gag- ros

Sarcoma

Abl

Abelson murine leukemia

Mouse

P 90 p160 gag-abl

Pre B cell

leukemia

Ski

SKV

Chick

P 110 gag-ski-pol

Sarcoma

Erb-A

Avian erythroblastasis

Chick

P 75 gar-Erb-a

Erythro-

blastasis

Erb-B

Avian erythroblastasis

Chick

Gp 65 Erb-B

Sarcoma

Fms

McDonough SM-Fe-Sv

Cat

Gp 180 gag-fus

Sarcoma

Fos

FBJ (Finkel-biskis-jinkins) MSV

Mouse

Pp55-fos

Osteo-

†sarcoma

Mos

Maloney MSV

Mouse

P 37 Env Mos

Sarcoma

Sis

Simian sarcoma virus

Monkey

P 28 env-bis

Sarcoma

 

Parody-irgens Fe-Sv

Cat

P 76 gag-sis

Sarcoma

Myc

Mc 29

Chick

P 100 gag-myc

Sarcoma.

meylectoma, carcinoma

Myb

Avian Myeloblastasis V

Chick

P 45 Myb

Myeloblastasis

 

AMV E 26

Chick

P 135gag-mys ets

Myeloblastasis, erythroblastasis

Rel

Retinoendotheliosis V REV

Turkey

P 64 rel

Reticulo-

endotheliosis

Kif

HZ4 fe-Sv

Cat

P 80 gag-kit

Sarcoma

Raf

3611-msv

Cat

P 80 gag-kit

Sarcoma

H-ras

Harvey MSV

Rat

Pp 21 ras

Sarcoma

and erythroleukemia

 

RASV

Rat

P 29 gag-ras

Sarcoma?

K-ras

Kirsten MSV

Rat

Pp 21 ras

Sarcoma. Erythroleukemia

Ets

AMV-E2b

Chick

P 135 gag-myb-ets

Same as myb

 

 

 

 

 

 

 

 

 

 

 

 

 

A list of few Cellular Oncogenes:

(Sangerís lab lists about 125-135 cancer genes).

†††††

Oncogene

Cellular

†Location

Function

Class I proteins:

 

 

Src

PM

Tyrosine specific protein kinase

Yes

Pm

Tyrosine specific protein kinase activity

Fgr

?

††††††††††† Same as above

Abl

PM

††† Same as the above

Fps (fes)

Cytoplasm

††† Same

Erb-B

Transmembrane protein

EGF receptor /tyrosine specific protein kinase

Fms

PM-TM

CSF-1 receptor/ tspk

Ros

PM-TM

TSPK (Tyrosine specific protein kinase)

Kit

PM

 

Mos

Cytoplasm

Serine /threonine protein kinase

Raf (mil)

---

Serine /threonine protein kinase

Class III GTP

binding factors;

 

 

H-RAS

PM

Guanine binding with GTPase activity

K-ras

PM

GTP binding with GTPase activity

Class III growth factors:

 

 

Sis

Secreted

Derived from platelet derived growth factor (PDGF)

Class Ii nuclear proteins

 

 

Myc

Nucleus

 

Myb

Nucleus

 

Fos

Nucleus

 

Ski

Nucleus

 

CLASS V HORMONE RECEPTORS:

 

 

Erb-A

Cytoplasm

Thyroid hormone receptors

Unclassified

Rel etc