KURSK STATE MEDICAL UNIVERSITY

DEPARTMENT OF MICROBIOLOGY

HIV- Human Immunodeficiency

VirusStudent:Guilherme L. Paschoalini

Group: 29 – 2nd year

KURSK - 2014

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.

CLASSIFICATIONFamily: Retroviridae

Subfamily:OrthoretrovirinaeGenus: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

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

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.

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

FACTORS OF VIRULENCEEnzymes: 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

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 needlesIII. Organ transplacentationIV. 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.

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

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.

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.

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 manifestation4. Terminal stage (AIDS)

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, p242. HIV-2: antibodies to gp36, gp105, gp140

PREVENTIONDetermination 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

TREATMENTDrugs 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

Thank you