INTRODUCTION TO HUMAN IMMUNODEFICIENCY VIRUS (HIV)
⇒ HIV, the Human Immunodeficiency Virus is the causative agent of AIDS, the Acquired Immune Deficiency Syndrome.
⇒ This syndrome was first observed in 1981 & isolated in 1983.
⇒ HIV is the member of Lentivirus Genus of the Family Retroviridae.
⇒ Members of Retroviridae possess reverse transcriptase (RNA directed DNA polymerase) enzyme which prepares the DNA copy of RNA genome (of the virus) in the host cell.
MORPHOLOGY OF HUMAN IMMUNODEFICIENCY VIRUS
⇒ HIV is a spherical, enveloped virus, core virus is surrounded by a nucleocapsid composed of protein & contains a lipoprotein envelope,
⇒ Size – 90-120 nm in diameter.
⇒ Genetic Material – Single-stranded positive-sense RNA genome ((+) ssRNA).
⇒ The Envelope glycoprotein spikes are present on the surface of the virus, binds to the CD4 receptors on susceptible host cells.
CLASSIFICATION OF HUMAN IMMUNODEFICIENCY VIRUS
⇒ Based on the genome organization, HIV has been classified as HIV-1 & HIV-2.
⇒ Genes coding for structural protein:-
- HIV genome consists of the three structural genes – gag, pol & env.
- The gag gene codes for the Core & Shell of the virus.
- The pol gene codes for the reverse transcriptase enzyme & other enzymes like protease and endonuclease. The sequence of pol gene is highly conserved.
- The env gene codes for the envelope glycoprotein.
- HIV-1 strains have been classified into 3 groups, based on sequence analyses of their gag & env genes sequence as M, N & O.
- Group M consists 10 subtypes as A, B, C, D, E, F, G, H, J & K (A-K except I).
- The subtype C is the most prevalent in India & China.
- HIV-2 strains have been classified into 8 groups, based on the env genes sequence as A, B, C, D, E, F, G, and H.
- The envelope glycoprotein gp160, coded by env gene, in cleaved into the two envelope components: gp120 – forms the surface spikes, and gp41 (in HIV-1) & gp36 (in HIV-2) – the transmembrane anchoring protein.
- The surface spikes glycoprotein gp120 is the major envelope antigen.
⇒ Non-Structural & regulatory genes:-
- The following five genes are present both in HIV 1 & HIV 2 viruses –
- tat (trans-activating gene) – enhances the expression of all viral genes.
- nef (negative factor gene) – regulates viral replication.
- rev (regulator of virus gene) – enhances the expression of the structural protein.
- vif (viral infectivity factor gene) – influences the infectivity of the viral particle.
- vpr – stimulates promoter region of the virus.
- Vpu (only in HIV-1) & vpx (Only in HIV-2) – enhances maturation & release of progeny virus from cells.
RESISTANCE SHOWN BY HUMAN IMMUNODEFICIENCY VIRUS
⇒ HIV is thermolabile, being inactivated in 10 minutes at 60o Celsius and in few seconds at 100o
⇒ HIV is inactivated by treatment with 35% isopropyl alcohol, 70% ethanol, 0.5% Lysol, 3% H2O2 or 10% bleach at 37o
⇒ A 2% glutaraldehyde solution is used to treat contaminated medical instruments.
⇒ Extreme low pH (1) or extreme high pH (13-14) can inactivate the virus.
MODES OF TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS
- Sexual contact
- Parenteral transmission
- Perinatal transmission
DISEASE CAUSED BY HUMAN IMMUNODEFICIENCY VIRUS
⇒ HIV causes Acquired immune deficiency syndrome (AIDS).
⇒ HIV virus attaches to T-lymphocytes at CD4 receptor via body fluids.
⇒ Most of the patients with HIV disease die of infection other than HIV e.g. opportunistic infections & malignancies.
⇒ The commonly associated opportunistic infections and malignancies associated with HIV are:-
- Bacterial – Tuberculosis, Typhoid, Gonorrhea etc.
- Viral – CMV, HSV, EBV, HHV, HBV etc.
- Fungal/Mycotic – Candidiasis, Cryptococcosis, Histoplasmosis, Aspergillosis etc.
- Parasitic – Toxoplasmosis, Cryptosporidiosis etc.
- Malignancies – Kaposi’s sarcoma, Non-Hodgkin’s lymphoma etc.
CLINICAL FEATURES OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION
⇒ The incubation period for AIDS varies from 6 months to 14 years, with an average of 6 years.
⇒ Initial symptoms include:-
- Low-grade fever
LABORATORY DIAGNOSIS OF HUMAN IMMUNODEFICIENCY VIRUS
⇒ The Lab Diagnosis of HIV infection includes the following tests:-
- SPECIFIC TESTS:-
- Virus isolation – patient’s lymphocytes are co-cultivated with uninfected human lymphocytes in the presence of interleukins-2.viral replication can be detected by demonstration of reverse transcriptase activity & presence of viral antigen.
- Detection of viral nucleic acid by polymerase chain reaction (PCR).
- Demonstration of viral specific antibodies.
- Electron Microscopy
- Phase Contrast Microscopy
- NON-SPECIFIC / SUPPLEMENTAL TESTS
- Western Blotting Assay
- Karpas test
PROPHYLAXIS FOR THE HUMAN IMMUNODEFICIENCY VIRUS INFECTION
⇒ The use of condoms can prevent the transmission then of the virus through sexual route.
⇒ Contaminated syringes or needles should not be shared.
⇒ All blood & blood products are to be screened for HIV.
TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION
⇒ Specific treatment with antiretroviral drugs is the mainstay in the management of HIV infection
⇒ Prompt diagnosis & appropriate treatment of opportunistic infection & tumors in the early stage of AIDS is very useful in restoring the normal life in between the episodes of illness.