- Slides: 30
HIV • HIV stands for Human Immunodeficiency Virus. • IT is a lentivirus. (a member of the retrovirus family) • HIV is the virus that causes AIDS. (Acquired Immunodeficiency Syndrome). • HIV is present as both free virus particles and virus within infected immune cells.
HISTORY • HIV is thought to have originated in non-human primates in sub-Saharan Africa and transferred to humans early in the 20 th century. • Chimpanzees to human
STRUCTURE OF HIV • HIV virus particle under a electron microscope, would look something like this • The size of the particle is around 0. 0001 mm
STRUCTURE OF HIV • There are two main parts • VIRAL MEMBRANE • INNER CORE • .
VIRAL MEMBRANE • The viral membrane encloses the particle, and has about nine or ten gp 160 (gp 120+gp 41) spikes embedded in it which are involved in binding and membrane fusion when the virus particle attaches to a cell.
INNER CORE • The inner core of a mature HIV particle is a shell made of • VIRAL RNA and • some ENZYMES 1. Reverse Transcriptase, 2. Protease, 3. Integrase. • SOME PROTEINS
VIRAL RNA • HIV and other retroviruses keep their genetic information in RNA form. • Two identical strands of RNA are found in the particle. RNA molecules are naturally attracted to each other and form dimer
1. REVERSE TRANSCRIPTASE • The enzyme reverse transcriptase (RT) is unique to retroviruses such as HIV which transcribes RNA into DNA. With this enzyme HIV can create viral DNA after entering the cell, and the viral DNA can then go on to be integrated into the host genome. • HIV-1 RT is composed of two molecular subunits called p 66 and p 51. • In fact, p 51 is effectively just a "truncated" form of p 66, although the two proteins do actually fold up differently after production.
2. PROTEASE • Protease is vital to HIV function; • It helps to process the gag and pol proteins (at the same time as, or shortly after, the virus buds from the cell surface) into functional forms. • cut certain proteins at certain points: the gag and gag-pol proteins produced from the HIV genome are long things which are like HIV's proteins all connected one after the other, and protease is needed to make the vital snips to cut these large precursors into the right pieces.
3. INTEGRASE • Integrase is HIV's enzyme for • inserting the DNA version of its genome into the host cell's DNA. • It catalyses the "cut-and-paste" operation of snipping the host DNA and attaching the proviral genome to the snipped ends
HIV GENOME • The full HIV genome is encoded on one long strand of RNA. (In a free virus particle, there actually two separate strands of RNA, but they're exactly the same!) • When the virus is integrated into the host's DNA genome then its information too is encoded in DNA.
HIV GENOME The genes in HIV's genome are as follows: • gag (coding for the viral capsid proteins) • pol (notably, coding for reverse transcriptase) • gag and pol together can be expressed in one long strand called "gag-pol") • env (coding for HIV's envelope-associated proteins) • And the regulatory genes: tat, rev, nef, vif, vpr, vpu
HIV TROPISM The term viral tropism refers to which cell types HIV infects. HIV can infect a variety of immune cells such as • CD 4+ T cells, • mcarophages, and • microglial cells • Cell carrying the CD 4 protein (CD 4+ cell) on its surface is susceptible, CD 4 is the main receptor for HIV. • T cells and macrophages, both of which are CD 4+, are two important targets for HIV Virus T-Cell HIV Infected T-Cell New HIV Virus
HIV LIFE-CYCLE • Reverse Transcriptions Act Here 6. Assembly & Budding Protein Inhibitors Act Here 2. Reverse Transcription 1. Attachment 7. Maturation 1. Entry 3. Integration 5. Translation 4. Transcription
1. ATTACHMENT and ENTRY • • • GLYCOPROTEINS (gp 160 • spike contains binding domains) gp 120 (strucral change, exposing chemokines binding sites) gp 41 RECEPTORS (CD 4 and a chemokine receptor; CCR 5) VIRAL ENVELOPE HIV CAPSID
2. REVERSE TRANSCRIPTION • Reads the sequence of viral RNA. • Transcribes into a complementary DNA sequence. • Without reverse transcriptase, the viral genome couldn't reproduce. • Reverse transcriptase sometimes makes mistakes in reading the RNA sequence. • Viruses produced in a single infected cell are not alike. Instead, differences occur in their surface molecules. Reverse Transcription
3. INTEGRATION • Once the viral RNA has been reverse-transcribed into a strand of • DNA, the DNA can then be integrated (inserted) into the DNA of the lymphocyte. • The virus has its own enzyme called "integrase" that facilitates incorporation of the viral DNA into the host cells DNA. • The integrated DNA is called a provirus.
4. TRANSCRIPTION • When the lymphocyte is activated, transcription of the viral DNA begins, resulting in the production of • multiple copies of viral RNA. • Transcriptase Transcription
5. TRANSLATION • This RNA codes for the production of the viral proteins and enzymes • And will also be packaged later as new viruses. • Only 9 genes in the HIV RNA, code to produce structural proteins such as the viral envelope and core plus enzymes (reverse transcriptase, integrase, protease). • Viral RNA is translated into a polypeptide sequence • Sequence is assembled in a long chain that includes several individual proteins (reverse transcriptase, protease, integrase).
6. ASSEMBLY & BUDDING • A new virus is assembled from RNA and short pieces of protein. • The • virus pushes (buds) through the membrane of the cell, wrapping itself in a fragment of the cell membrane and pinching off from the infected cell • Eventually, the lymphocyte is destroyed. Budding new viruses
7. MATURATION • To be able to infect other cells, the budded virus must be matured. • It becomes mature when another HIV enzyme • protease cuts longer polypeptide chain into its Viral individual enzyme components. • Then these enzymes become functional, and facilitate the production of new viruses. Proteins cut and packaged with RNA
CONTINUE……… • The thousands of new viruses produced by each infected cell which infect other lymphocytes and can destroy them • well. as • Within a few days or weeks, the blood and genital fluids contain many viruses, • The number of CD 4+ lymphocytes may be reduced Because the number of viruses in blood and genital fluids is so large • Soon after HIV infection, newly infected people can readily spread HIV to other people.
TRANSMISSION OF INFECTION • Unprotected sexual relations mainly through semen, vaginal secretions, when the mucous membrane lining the mouth, vagina, penis, or rectum is exposed to contaminated • body fluids • Blood or blood product by Injection, blood transfusions, sharing of needles, or an accidental prick with an HIVcontaminated needle • Mother-to-child (During pregnancy and by breast feeding) • Tears • Urine • Saliva
SYMPTOMS • Within a few weeks, fever, rashes, swollen lymph nodes, fatigue. • HIV can also cause symptoms when it directly infects parts of the body: • Brain: Memory loss, difficulty in thinking and concentrating, eventually resulting in dementia, as well as weakness, tremor, or difficulty in walking • Kidneys: Swelling in the legs and face, fatigue, and changes in urination (more common in blacks than in whites) • Heart: Shortness of breath, cough, wheezing, and fatigue (uncommon) • Genital organs: Decreased levels of sex hormones, which, for men, leads to a decreased interest in sex
DIAGNOSIS • • Simple Screening tests Enzyme-linked immunosorbent assay (ELISA): Newer rapid screening tests: specific test such as the Western blot
TREATMENT ANTIRETROVIRAL DRUG 1. Reverse transcriptase inhibitors • AZT-like Drugs Inhibit Reverse Transcription 2. Protease inhibitors 3. Fusion inhibitors 4. Integrase inhibitors
ANY QUESTION ?
HAVE A NICE DAY Presented By: AMAAN ALI BS