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Retro Virus Human Immunodeficiency Virus (HIV)

Retro Virus Human Immunodeficiency Virus (HIV). Shaili shah MD 3 Roll #: 1278. Table of Content. Introduction History Replicative cycle Transmission and Epidemiology Pathogenesis and Immunity Clinical Findings Lab Diagnosis Treatment and Prevention Conclusion. Introduction.

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Retro Virus Human Immunodeficiency Virus (HIV)

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  1. Retro VirusHuman Immunodeficiency Virus (HIV) Shaili shah MD 3 Roll #: 1278

  2. Table of Content • Introduction • History • Replicative cycle • Transmission and Epidemiology • Pathogenesis and Immunity • Clinical Findings • Lab Diagnosis • Treatment and Prevention • Conclusion

  3. Introduction What is HIV? • H– Human – This particular virus can only infect human beings. • I – Immunodeficiency–weakens your immune system by destroying important cells that fight disease and infection. • A "deficient" immune system can't protect you. • V– Virus – A virus can only reproduce itself by taking over a cell in the body of its host. • A virus that infects only humans by destroying the immune system.

  4. Continue… • HIV is a “lentivirus” • In turn part of a larger group of viruses known as retroviruses. • The name 'lentivirus' literally means 'slow virus' because they take such a long time to produce any adverse effects in the body. • Positive sense (ss) RNA virus, diploid, and non-segmented. • Infects and destroys CD4+ cells, therefore body can no longer defend itself against infection. • Two types of HIV: • HIV – 1: causes almost all the cases of AIDS worldwide • Most transmissible • HIV – 2: causes and AIDS-like illness • Uncommon in North America

  5. Continue… • Three stages of HIV infection have been described: • primary infection occurs within weeks of acquiring the virus, often is characterized by a flu- or mono-like illness that generally resolves within weeks. • Secondary infection is the stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of 8 to 10 years. • Tertiary infection which is the last stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, leading to acquired immunodeficiency syndrome (AIDS). • Caused by both types, HIV – 1 and HIV - 2

  6. History • HIV has existed since at least the mid- 1900s. • Rare types of pneumonia, cancer, and other illnesses were being reported by doctors, among a number of homosexual males. • In 1982 public health officials began to use the term "acquired immunodeficiency syndrome," or AIDS, to describe the occurrences of opportunistic infections. • In 1983, scientists discovered the virus that causes AIDS was non other than HIV. • HIV was at first named HTLV-III/LAV (human T-cell lymphotropic virus-type III/lymphadenopathy-associated virus) by an international scientific committee. • The name was later changed to HIV (human immunodeficiency virus). • For many years scientists theorized as to the origins of HIV and how it appeared in the human population, most believing that HIV originated in other primates • In 1999, discovered the origins of HIV-1, the predominant strain of HIV in the developed world. • A subspecies of chimpanzees native to west equatorial Africa had been identified as the original source of the virus. • The most interesting lentivirus in terms of the investigation into the origins of HIV is the Simian Immunodeficiency Virus (SIV). • Scientists believed 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. • Over decades, the virus slowly spread across Africa and later into other parts of the world.

  7. Replicative Cycle Entry Reverse Transcription Integration Transcription Assembly Budding

  8. Continue… • Entry: Proteins, called envelope proteins, embedded in the outer membrane of the HIV virion bind to receptors CD4 and CCR5 which are found on the surface of target cells. Binding of the HIV envelope protein to CD4 and CCR5 allows the HIV outer membrane to fuse with the cell’s outer membrane and the contents of the virus particle to enter the cell. • Reverse Transcription: A special enzyme called reverse transcriptasechanges the genetic material of the virus, so it can be integrated into the host DNA. • Integration: the viral DNA enters the nucleus of the host and becomes integrated into the host’s DNA. An enzyme called integraseintegrates the viral DNA into the cell’s DNA. The cell is infected for the rest of the life. The integrated viral DNA is referred to as a provirus. • Transcription:When the host cell becomes activated, and the virus uses your own enzymes to create more of its genetic material—along with a more specialized genetic material which allows it make longer proteins. • Assembly: A special enzyme called protease cuts the longer HIV proteins into individual proteins. When these come together with the virus’ genetic material, a new virus has been assembled. • Budding: This is the final stage of the virus’ life cycle. In this stage, the virus pushes itself out of the host cell, taking with it part of the membrane of the cell. This outer part covers the virus and contains all of the structures necessary to bind to a new CD4 cell and receptors and begin the process again.

  9. Transmission • HIV is spread when blood, semen, or vaginal fluids from an infected person enter another person's body, usually through • sexual contact, • from mother to baby during birth, or • from sharing needles when injecting drug.

  10. epidemiology • The earliest known case of infection with HIV-1 in a human was detected in a blood sample collected in 1959 from a man in Kinshasa, Democratic Republic of the Congo. • African American face the most severe burden of HIV. • Gay, bisexual, and other men who have sex with men, particularly young African American are most seriously affected by HIV. • There were 35.3 million people living with HIV/AIDS worldwide in 2012 • 1.6 million people died of AIDS-related illnesses (2012). • More than 1.1 million people in United States are living with HIV infection, and almost 1 in 6 (15.8%) are unaware of their infection. • Estimated 1 million people aged 13 to 24 years old are living with HIV infections. Figure 5: Estimated New HIV Infections in the United States, 2010, for the Most Affected Subpopulations.

  11. Continue….

  12. Pathogenesis and immunity • Infects humans when it comes in contact with tissues such as those that line the vagina, anal area, mouth, eyes, or through a break in the skin. • After HIV is in the body, it starts to destroy CD4+ cells • which are white blood cells that help the body fight infection and disease. • Below 200 cells/mm3 or 14% • Incubation period: • Initial - 2 to 4 weeks

  13. Clinical findings • Clinical Latency Stage: • aka “asymptomatic HIV infection” or “chronic HIV infection” • Period of virus development at very low levels, without producing symptoms • People who are infected with HIV experiences no HIV-related symptoms or only mild ones • Progression to AIDS: symptoms • Rapid weight loss • Recurring fever or profuse night sweats • Extreme tiredness • Prolonged swelling of lymph glands • Diarrhea (last more than a week) • Sored of mouth, anus, or genitals • Pneumonia • Red, brown, pink, or purplish blotches on or under the skin or inside mouth, nose, eyelids • Memory loss, depression and other neurological disorders Early Stage: few days to several weeks • Fever • Headache • Swollen glands • Sore throat • Nausea and vomiting • Rash • Fatigue • Muscle and joint aches

  14. Lab diagnosis • Screening – ELISA or LATEX Agglutination • Most commonly done to detect HIV antibodies in patient’s serum • Look for p24 • Conformation using second blood sample • Western blot for antibodies specific for HIV or Immunofluorescence • RT – PCR • Detection of virus in blood (viral load) • HIV DNA PCR (polymerase chain reaction) • Qualitative to detect HIV infection in newborns of HIV+ mothers • Quantitative HIV DNA PCR to determine viral load to assess treatment. • Culture of HIV (with Antigen Detection in culture) • HJIV infection in newborns whose mothers are HIV+ • To assess drug resistance • CD4:CD8 T-cell Ratio • To evaluate the progression of disease

  15. Treatments • No vaccine, yet! • Recently babies born in Canada to AIDS-infected mothers received new vaccine within hours of entering the world and declared HIV-free, however medical officials are optimistic! • Antiretroviral Therapy (ART) • Most effective treatment • A combination of several medicines that aims to control the amount of virus in the body. • RT (Reverse Transcriptase) Inhibitors • Nucleoside – Abacavir, Amtricitaibine, Tenofovir • Non-nucleoside – Efavirenz, Etravirine, Nevirapine • Fusion Inhibitors • CCR5 receptor antagonist • Integrase inhibitors - Raltegravir

  16. prevention • Screening • Education • Infection control and vaccine development • Safer sex, such as use of condom • If HIV (+) do not donate blood, plasma, semen, body organs or body tissues • Use of clean needles and equipment • Don’t share it with others

  17. Conclusion Case: A 37-year-old gay man presented with a 3-day history of headache, fever, myalgia, and sore throat. The patient had previously been in good health except for an appendectomy at age 6. He was living with his partner who had had fatigue, night sweats, and weight loss for the past 2 years. They last had unprotected intercourse 2 weeks ago. On physical examination, the patient had a temperature of 38°C. There was a finemaculopapular rash. His neck was supple, but submandibular and axillary nodes were enlarged. A few small ulcers were noted on the palate. The results of an HIV-1 ELISA were negative, but a p24 antigen test was positive at greater than 200 pg/mL. The CD4+ count was 492 cells/mm3. A diagnosis of primary HIV infection was made, and the patient was treated with acetaminophen. His symptoms resolved over the next 4 weeks and the CD4+ count stabilized at approximately 650 cells/mm3. The results of an ELISA turned positive, and the p24 antigen assay became negative. Therefore, • If HIV isn’t treated, most people gets AIDS within 10 to 12 years after the initial infection. • Since the beginning of the epidemic, almost 75 million people have been infected with HIV and about 36 million people have died with HIV. • Immune system can clear most viruses out of the body, however that isn't the case with HIV • The human immune system can't seem to get rid of the virus meaning that once you have HIV, you have it for life.

  18. References • MedicineNet- http://www.onhealth.com/human_immunodeficiency_virus_hiv_aids/article.htm • What is HIV/AIDS 101. (2014) - http://aids.gov/hiv-aids-basics/hiv-aids-101/what-is-hiv-aids/ • HIV life-cycle - http://aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/hiv-lifecycle/ • The Aaron Diamond AIDS Research Center - http://www.adarc.org/hiv_replication_632.html • The Aids Institute, “ Where did HIV come from?”. - http://www.theaidsinstitute.org/education/aids-101/where-did-hiv-come-0 • HIV and AIDS Health Center - http://www.webmd.com/hiv-aids/tc/human-immunodeficiency-virus-hiv-infection-medications • Statistics (epidemiology) - http://www.who.int/gho/hiv/en/ • The Washington Times (2014), “Three babies given vaccine hours after birth considered HIV-free” - http://www.washingtontimes.com/news/2014/jul/1/three-babies-given-vaccine-hours-after-birth-consi/

  19. Thank you!

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