Biomedical Engineering Reference
In-Depth Information
New progency virus
particles containing
reverse transcriptase
Single-stranded RNA retrovirus
RNA
Capsid
Plasma membrane of host cell
Envelop
8
Reverse
transcriptase
enzyme
1
7
Cytosol
2
Envelope proteins
Capsid protein
Reverse transcriptase
RN A
RNA
6
6
5
1. Cell entry and loss of envelop
2. Virus capsid loss
3. Synthesis of DNA/RNA & a DND/DNA double
helix by reverse
4. Integration of DNA copy into host chromosome
5. Transcription by host cell RNA polymerase
makes many RNA copies
6. Translation
7. Assembly
8. Viral budding
DNA
Integrated DNA
of virus
3
DNA
DNA
4
Protein of
host cell
chromosomes
Figure 5.8 Life cycle of retrovirus [147] .
5.4.1.3 Structure of Virus and Its Genome
Retroviruses are complex particles that contain two copies of a positive strand RNA
genome condensed within a core containing several viral proteins; they also are enclosed
in a lipid envelope that contains both viral and host cell proteins. The viral RNA genome
is about 9 kb long. Mainly, it contains three genes, in order gag, pol, and env that are
bound by terminal cis -acting control regions at either end of the genome. These cis act-
ing regions include, at either end of the genome, the same long terminal repeat (LTR)
region which contains a subregion that has transcriptional enhancer and promoter activi-
ties following polyadenylation site. There is a splice donor site between the 5 LTR and
the gag gene and a splice acceptor site in the 3 end of the pol gene upstream of the env
gene and the splice donor site is followed by a region called Y, that overlaps the 5 end
of gag and is required in cis for encapsidation of the viral RNA ( Fig. 5.9 ) [149, 150].
Gag codes for three structural proteins: (1) the matrix (MA), (2) the capsid (CA),
and (3) the nucleocapsid (NC). Gag is translated as a precursor protein and can be
posttranslationally modified (myristylation). Generally, retroviruses express other
gag proteins that play a role in correct particle shaping (p6 in HIV).
Pro codes for an aspartic protease that is most essential for viral infectivity
through particle maturation. Pol codes for at least two enzymes: (1) the RT and (2)
the integrase (IN). Pol is produced as a fusion protein with the gag precursor.
Env encodes a membrane-bound glycoprotein that is mainly responsible for the
recognition of the target cell. The viral envelope generally is composed of two viral
env gene products: surface glycoprotein (SU) and a membrane-spanning domain
(TM). Exposed on the outside of the virion, env proteins are arranged in trimers,
being anchored within the viral envelope originating from the cellular lipid bilayer.
 
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