HUMAN IMMUNODEFICIENCY VIRUS Year 4 Paediatrics Notes

HUMAN IMMUNODEFICIENCY VIRUS Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Agisa -- Slide 1 HUMAN IMMUNODEFICIENCY VIRUS MBCB Slide 2 Introduction The human immunodeficiency viruses (HIV) are two species of Lentivirus (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS),[ a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype Slide 3 The first news story on "an exotic new disease" appeared May 18, 1981, in the gay newspaper New York Native. AIDS was first clinically observed in 1981 in the United States. The initial cases were a cluster of injection drug users and gay men with no known cause of impaired immunity who showed symptoms of Pneumocystis pneumonia (PCP or PJP, the latter term recognizing that the causative agent is now called Pneumocystis jirovecii), a rare opportunistic infection that was known to occur in people with very compromised immune systems. Soon thereafter, researchers at the NYU School of Medicine studied gay men developing a previously rare skin cancer called Kaposi's sarcoma (KS).Many more cases of PJP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak. Slide 4 Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III).\nHIV-1 is more virulent and more infective than HIV-2, and is the cause of the majority of HIV infections globally.\nThe lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa Slide 5 Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa, and are believed to have transferred to humans (a process known as zoonosis) in the early 20th century. HIV-1 appears to have originated in southern Cameroon through the evolution of SIVcpz, a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes). The closest relative of HIV-2 is SIVsmm, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in littoral West Africa (from southern Senegal to western Côte d'Ivoire) Slide 6 In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk.[7][8][9][10] Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. Research has shown (for both same-sex and opposite-sex couples) that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load. Slide 7 HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells.[HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS. Slide 8 HIV is a member of the genus Lentivirus,[15] par Slide 9 HIV STRUCTURE Slide 10 HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120 nm, around 100,000 times smaller in volume than a red blood cell.[23] It is composed of two copies of positive-sense single-stranded RNA that codes for the virus' nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24 The single-stranded RNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease and integrase. A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle Slide 11 The term viral tropism refers to the cell types a virus infects. HIV can infect a variety of immune cells such as CD4+ T cells, macrophages, and microglial cells. HIV-1 entry to macrophages and CD4+ T cells is mediated through inter