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Microbiology of HIV VIRUSES
1. KURSK STATE MEDICAL UNIVERSITY
DEPARTMENT OF MICROBIOLOGY
HIV- Human
Immunodeficiency
Virus
Student:Guilherme L. Paschoalini
Group: 29 – 2nd year
KURSK - 2014
2. HIV
The human immunodeficiency virus is a lentivirus that causes
the acquired immunodeficiency syndrome (AIDS), a condition
in humans in which progressive failure of the immune
system allows opportunistic infections and cancers to prosper
Unlike some other viruses, the human body cannot get rid of
HIV. That means that once you have HIV, you have it for life.
Scientists identified a type of chimpanzee in West Africa as
the source of HIV infection in humans. They believe that the
chimpanzee version of the immunodeficiency virus (called
simian immunodeficiency virus, or SIV) most likely was
transmitted to humans and mutated into HIV when humans
hunted these chimpanzees for meat and came into contact
with their infected blood. HIV was first described in USA in
1981 amongst homosexuals, haitians and heroine addicts.
3. CLASSIFICATION
Family: Retroviridae
Subfamily:Orthoretrovirinae
Genus:Lentivirus
Species: HIV 1 / HIV 2
HIV 1- Isolated in America, Europe & central Africa
HIV 2- In West Africa – Less virulent and not spread as
widely and rapidly as HIV 1
4. MORPHOLOGY
It is roughly spherical - diameter of about 120 nm
Composed of two copies of positive single stranded RNA
(Held together by protein P7) enclosed by a
conical capsid composed of viral protein P24
Very high genetic variability
The RNA genome consists of 9 genes - Three of these
genes: gag, pol, and env, contain information needed to
make the structural proteins for new virus particles.
Inside of capsid are three enzymes required for HIV
replication: reverse transcriptase, integrase and protease.
A matrix composed of the viral protein P17 surrounds the
capsid ensuring the integrity of the virion particle
The matrix is surrounded by phospholipids – 2 layers –
Embedded by 70 copies of a complex HIV protein
(glycoprotein) – Spikes: 2 units – Gp41 and Gp120
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7. RESISTANCE
HIV doesn't survive well outside the body
It is inactivated within 10 minutes at temperature 50ºC and
within seconds in temperature100ºC; by treatment with
alcohol 50%, 35% isopropanol, 0.5% formaldehyde, 0-3%
hydrogen peroxide
May survive up to 7 days in dry blood
Virus is inactivated under extreme changes of pH in acidic
and alkaline medium.
8. CULTIVATION
Culture of HIV is difficult
Is not done frequently because of the risk involved
The virus is cell associated - Patient’s peripheral blood
mononuclear cells (CD4, T-cells, macrophages) are co-
cultivated with those of uninfected human blood in the
presence of PHA and interleukins 2
Cytolysis and syncitia formation
The fluid of culture is tested to demonstrate the reverse
transcriptase activity
9. FACTORS OF VIRULENCE
Enzymes:
Revere transcriptase - enzyme used to generate complementary DNA
(cDNA) from an RNA template
Protease - cleaves newly synthesized polyproteins at the appropriate
places to create the mature protein components of an infectious
HIV virion. Without effective HIV protease, HIV virions remain
uninfectious.
Ribonuclease - catalyzes the cleavage of RNA
Integrase - main function is to insert the viral DNA into the host
chromosomal DNA
Inner core capsid protein – Forms the capsid
Nucleic acid-binding proteins
Glycoproteins
Gp120 – Constains conserved highly regions that binds to CD4
proteins of host cells – Attachment in host cells
Gp41 – Analogous to the fusion – Penetration in host cells
10. EPIDEMIOLOGY
TRANSMISSION – HIV is transmitted through blood,
semen, vaginal fluid and from infected mother to her
child
I. Sexual contact – HIV is predominantly a sexual
transmitted disease
II. Contaminated needles
III. Organ transplacentation
IV. Blood or blood products
• It is not spread by air or water, vector, saliva, tears, or
sweat, casual contact like shaking hands or sharing dishes,
closed-mouth or “social” kissing
• HIV risk factors and routes of transmission apply to
everyone equally, some people are at higher risk because of
where they live and who their sex partners are.
11. Approximately 35.3 million people are living with HIV
globally.
Sub-Saharan Africa is the region most affected - This means
that about 5% of the adult population in this area is infected
A reconstruction of its genetic history shows that the HIV
pandemic almost certainly originated in Kinshasa, the capital
of the Democratic Republic of the Congo, around 1920.
30 million deaths till now
12.
13.
14. PATHOGENESIS
Receptor for virus is CD4 receptor. Therefore virus may infect
any cells having CD4 receptors on the surface.
The specific binding site to the virus is enveloped
glycoprotein (Gp120).
Infection is transmitted when virus enters the blood or tissues
of a person and comes into contact with suitable host cells,
principally CD4 lymphocytes.
Double stranded DNA transcript to the viral DNA and
integrated into genome of infected cells causing latent
infection. From time to time lytic infection is initiated
releasing progeny virions which infect other cells.
Long and variable incubation period of HIV infection is
because of the latency.
The primary pathogenic mechanism is damaged to T-
lymphocytes (CD4). CD4 cells decrease in numbers and the
ratio of CD4 over CD8 is reversed.
15. Infected CD4 cells do not appear to release normal
amount of interleukins, interferons and other
lymphokines. Therefore, immune state of a person
decreases
Though the major damage is to cellular immunity,
humoral mechanism is affected.
Patients are unable to respond to new antigens. An
important feature to HIV infection is the polyclonal
activation of B-lymphocytes.
This leads to hyper-γ-globulinaemia. All classes of
immunoglobulins are involved but level of Ig G and Ig A
particularly rose. In infants and children Ig M is
elevated. Hyper-γ-globulinaemia is more of hindrance
than help because it is composed of mainly useless Ig.
Monocyte, macrophage function also affected. As a
result chemotaxis and antigen presentation and
intracellular killing by these cells are diminished. NK
cells are also affected by HIV leading to state of innate
immunity.
16. CLINICAL MANIFESTATION
HIV infection damages respiratory system, pneumonia,
bronchitis, pleuritis may take place
CNS may be affected: meningitis, dementia etc.
GIT: enteritis, decrease body mass, diarrhea.
Malignancies: Carposious sarcoma, other tumors
HIV infection has 4 stages:
1. Incubation period (2-4weeks)
2. Stages of primary manifestation (years)
3. Stage of secondary manifestation
4. Terminal stage (AIDS)
17. LABORATORY DIAGNOSIS
Include test for immunodeficiency detection as well as
specific test for HIV
Immunological test - Total count of leukocyte and
lymphocyte (detect leucopenia), CD4 cells must be counted
and the ratio between CD4 and CD8 cells is detected,
counting of platelets and rising level of Ig G and Ig A
ELISA TEST
PCR
In order to prove presence of HIV, antibodies are
detected:
1. HIV-1: antibodies to gp41, gp120, gp160, p24
2. HIV-2: antibodies to gp36, gp105, gp140
18. PREVENTION
Determination of people of risk group
Identification of source of infection and
control
Health education – Sex should be practised by
avoiding exchange of body fluid (condoms are
utilized), using sterile needles and syringes
19. TREATMENT
Drugs of choice are inhibitors of reverse
transcriptase activity:
1. Nucleoside drag (inhibition of HIV-revertase ):
2. Retrovir (ZDV, AZT);
3. Videx (DDI);
4. Nivid (DDC);
5. Zerit (D4T);
6. Epivir (3TC)
Nonnucleoside drug:
1. Viramune;
2. Resariptor
Inhibitor of HIV-protease:
1. Crizivan