RETROVIRUSES

1.         Animal Retroviruses

a.         Many retroviruses cause natural cancer in their animal host.

b.         They also produce leukemia or sarcomata on inoculation into experimental animals.

c.            Although sarcoma viruses transform cells, most of the leukemia viruses do not.

d.            Sarcoma viruses:

i.          they readily transform cells in tissue culture, and produce solid tumors – fibrosarcomata – on inoculation into animals of the host species.

ii.          most are defective, and in order to replicate require the presence of a helper virus to supply the product of the defective gene.

iii.         the deletion often involves the env gene, and as a result sarcoma viruses are antigenically similar to the helper leukemia virus.

e.            Leukemia viruses:

i.          they produce leukemia on inoculation into animals.

ii.          most do not transform cells in tissue culture although some do.

iii.         they are not defective and generally replicate in tissue culture without CPE; cell growth and division are not affected.

2.            Genome structure

a.         gag gene: codes for the core protein antigens of the virus particle; these are cleaved from a larger precursor protein.

b.         pol gene: codes for the protein that is the reverse transcriptase.

c.         env gene: codes for the envelope glycoproteins of the virion.

d.         Long terminal repeat regions (LTR) at each end of the genome contain the powerful promoter and enhancer sequences responsible for the integration of provirus DNA transcript of the viral genome RNA into cellular chromosome.

e.            Additional regulatory genes: tat, rev, nef.

f.            Oncongenes:

i.          many retrovirus genomes have oncogenes incorporated into their structure.

ii.            oncogenes are genes whose expression can be associated with tumor production.

iii.            retroviruses cause cancer when their genome acquires cellular oncogenes by recombination.

iv.         this happens when RNA tumor viruses integrate in the form of provirus DNA into cellular chromosomes.

v.            oncogenes do not always give rise to carcinogenesis; they need to be activated and different mechanisms are required for this.

g.            Activation of viral oncogenes:

i.          virus promoter contain in the LTR regions of the retrovirus genome.

ii.          cellular promoter by translocation of the oncogene to a site on a chromosome with high activity.

iii.            cofactor such as a chemical carcinogen.

iv.            interaction with other oncogenes.

h.            Transmission from animal to animal:

i.            horizontal: spread of virus by close contact, possibly inhalation.

ii.          vertical: virus spreads from mother to offspring either in utero, at birth or via the mother’s milk.

iii.         genetic: virus is inherited as a provirus integrated into the chromosomes of the germ cells of parent animals.