Download Structure of retroviruses

Lec 8
virology
Retroviruses
*Introduction
The family Retroviridae includes a large number of disease-producing
animal viruses, several of which are of clinical importance to humans.
Retroviridae are distinguished from all other RNA viruses
by the presence of an unusual enzyme, reverse transcriptase, which
converts a single-stranded RNA viral genome into double-stranded viral
DNA.
* Structure of retroviruses :
1-Retroviruses are enveloped particles.
2-The viral envelope formed from the host cell membrane, contains a
complex HIV protein that arises through the surface of the virus particle
and appears as spiked knobs on electron micrographs of the virus.
3-The virion has a cone-shaped icosahedral core containing the major
capsid protein called p24.
4-Also found within the capsid are the enzymes reverse transcriptase ,
integrase (which are required for viral DNA synthesis and integration
into the host cell chromosome) and protease (essential for virus
maturation).
*Replication of retoviruses
Replication of retroviruses include several steps :
1-The conversion of a (+) strand RNA to a double-stranded DNA is
accomplished by an RNAdependent DNA polymerase, commonly
referred to as a (reverse transcriptase) that is contained in the virion.
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2-The resulting dsDNA becomes integrated into the cell genome by the
action of a viral integrase .
3- New viral mRNAs ( translation to structrural protein including
capsid )and progeny (+) strand RNA genomes are transcribed from this
integrated DNA by the host cell RNA polymerase.
4- Assembly the nucleucapsid .
5- Releasing of virus by budding .
Figure (1) Replication of retroviruses
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*Human immunodeficiency virus (HIV):
*Epidemiology:
Acquired immune deficiency syndrome (AIDS) was first reported in
theUnited States in 1981. The earliest cases of AIDS were seen in large
urban centers, such as Los Angeles, San Francisco, and New York City.
There were estimated to be about 2.5 million new infections worldwide
and 1.8 million deaths due to AIDS in 2009. Worldwide, new infections
are almost equally distributed between men and women,
Structure of HIV genome :
The HIV RNA genome contains three major genes: gag, pol, and
env . The gag gene encodes p17 (MA), p24 (CA), and p7 (NC) (core and
matrix proteins). The pol gene encodes reversetranscriptase, protease,
integrase, and ribonuclease. Finally, the env gene encodes gp41 (TM)
and gp120 (SU) (transmembrane and surface proteins).
Figure (2) genume structure of HIV
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*Transmission of HIV:
1- Sexual contact: HIV, present in both semen and vaginal
secretions is transmitted
2- Transfusions: HIV has been transmitted by transfusion with
blood, plasma, clotting factors, and cellular fractions of blood.
3- Contaminated needles: Transmission can occur by inoculation
with HIV-contaminated needles or syringes among drug users or
accidentally if a contaminated needle punctures the skin of a
health care worker.
4-Perinatal transmission: An HIV-infected woman has a 15 to
50 percent chance of transmitting the infection to her newborn,
either transplacentally, or during passage of the baby through
the birth canal.
*Pathogenesis:
1- After the acquisition of HIV, the initially infected
cells are generally macrophages within the genital tract .
2- HIV can then infect CD4+ lymphocytes moving through the
germinal center of lymph nodes.
3- The acute phase viremia is eventually reduced significantly
with the appearance of a HIV-specific cytotoxic T-lymphocyte
response .
4- Clinical complications of HIV infection during the latent period
During this period (of variable length but lasting on average about
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01years), there are multiple, nonspecific conditions, such as
generalized lymphadenopathy (swollen lymph nodes) diarrhea; chronic
fevers; night sweats; and weight loss. The more common opportunistic
infections, such as herpes zoster and, candidiasis may occur repeatedly
during this period as well as when patients progress to AIDS.
Laboratory identification
0- Demonstration of virus or virus components: Amplification of
viral RNA or DNA proviruses by the polymerase chain reaction
(PCR) technique . is the most sensitive method for early detection of
virus in blood or tissue specimens.
2-In addition, the circulating virus can be genotyped by sequencing,
3-ELISA (for enzyme-linked immunosorbent assay) testing for the CA
(p24) antigen in serum can detect otherwise undetectable infection in
individuals who are infectious by screening for anti-HIV antibodies.
Question expected about this lecture :
1- Explain the replication of HIV
2- compare between HIV and other RNA viruses in genume
structure
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