Chapter 11: Human Immunodeficiency Virus

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Questions and Answers

What does the acronym "AIDS" stand for?

Acquired Immune Deficiency Syndrome

What was the initial name given to the condition that is now known as AIDS?

Gay-Related Immune Deficiency (GRID)

What year was the first case study published that documented unusual cases of pneumonia in gay men?

1981

What is the name of the fungus that causes the pneumonia described in the first case study?

<p>Pneumocystis jirovecii</p> Signup and view all the answers

What type of cancer was also being reported in previously healthy gay men in 1981?

<p>Kaposi's sarcoma</p> Signup and view all the answers

What year did the CDC establish the name "Acquired Immune Deficiency Syndrome" (AIDS) for the disease?

<p>1982</p> Signup and view all the answers

What were the main routes of transmission for HIV that the CDC identified in 1983?

<p>Blood and blood products, sexual intercourse, and congenital transmission</p> Signup and view all the answers

HIV can be transmitted through respiratory secretions.

<p>False (B)</p> Signup and view all the answers

HIV can be transmitted through sharing food or water.

<p>False (B)</p> Signup and view all the answers

HIV can be transmitted through air.

<p>False (B)</p> Signup and view all the answers

HIV can be transmitted through personal contact.

<p>False (B)</p> Signup and view all the answers

What year did Pasteur Institute researchers Françoise Barré-Sinoussi and Luc Montagnier isolate a retrovirus from the lymph node of someone with AIDS?

<p>1983</p> Signup and view all the answers

What did Barré-Sinoussi and Montagnier name the retrovirus they isolated?

<p>Lymphadenopathy-associated virus (LAV)</p> Signup and view all the answers

What award did Barré-Sinoussi and Montagnier receive for their discovery of the retrovirus?

<p>The 2008 Nobel Prize in Physiology or Medicine</p> Signup and view all the answers

What other retrovirus did Robert Gallo describe in the same issue of Science as Barré-Sinoussi and Montagnier published their finding?

<p>Human T-lymphotropic virus type III (HTLV-III)</p> Signup and view all the answers

What year did Montagnier and Gallo announce that the two viruses they had discovered were in fact the same virus?

<p>1984</p> Signup and view all the answers

What name was officially given to the retrovirus in 1986?

<p>Human immunodeficiency virus (HIV)</p> Signup and view all the answers

What year was the blood test for HIV developed?

<p>1985</p> Signup and view all the answers

What year was the first antiretroviral drug, zidovudine (AZT), approved?

<p>1987</p> Signup and view all the answers

What year was the AIDS quilt put on display?

<p>1987</p> Signup and view all the answers

What year did Highly-Active Antiretroviral Therapy (HAART) become the standard treatment for HIV infection?

<p>1994</p> Signup and view all the answers

What year did the number of new AIDS cases decline for the first time?

<p>1996</p> Signup and view all the answers

What year did the CDC release a public service announcement to address fears about contracting AIDS?

<p>1983</p> Signup and view all the answers

What year did a vaccine effort using adenovirus to express HIV Gag, Pol, and Nef began?

<p>1986</p> Signup and view all the answers

What is the name of the vaccine strategy that has shown the most promise in combating HIV?

<p>Prime-boost strategy</p> Signup and view all the answers

What are the two types of HIV?

<p>HIV-1 and HIV-2 (C)</p> Signup and view all the answers

What is the name of the family to which HIV belongs?

<p>Retroviridae</p> Signup and view all the answers

What is the name of the genera to which HIV belongs?

<p>Lentivirus</p> Signup and view all the answers

What group of HIV-1 is responsible for the vast majority of infections worldwide?

<p>Group M (B)</p> Signup and view all the answers

What is the name of the HIV-1 subtype responsible for approximately 50% of infections?

<p>Subtype C</p> Signup and view all the answers

What HIV-1 subtype is most prevalent in Europe and the Americas?

<p>Subtype B</p> Signup and view all the answers

How many distinct groups of HIV-2 have been identified?

<p>Eight</p> Signup and view all the answers

What are the two groups of HIV-2 that are most prevalent?

<p>Group A and Group B</p> Signup and view all the answers

What are the rare groups of HIV-2?

<p>Groups C through I</p> Signup and view all the answers

HIV-2 subtypes are more common than HIV-1 subtypes.

<p>False (B)</p> Signup and view all the answers

What type of viruses were the source for the cross-species transmission that led to HIV-1 or HIV-2?

<p>Simian immunodeficiency viruses (SIVs)</p> Signup and view all the answers

What activity is believed to be responsible for transmitting SIVs to humans?

<p>Hunting bushmeat</p> Signup and view all the answers

What is the name of the former Belgian Congo city that is believed to be a point of origin for the spread of HIV-1?

<p>Leopoldville</p> Signup and view all the answers

What is the name of the river that a person infected with HIV through bushmeat hunting in Cameroon may have used to travel to the country where HIV-1 is believed to have originated?

<p>Sangha river</p> Signup and view all the answers

What is one of the main ways the virus is believed to have spread in Leopoldville?

<p>Reused needles</p> Signup and view all the answers

What year has a frozen plasma sample and preserved lymph node tissue from individuals living in Kinshasa, that tested positive for HIV-1, been isolated from?

<p>1959 and 1960</p> Signup and view all the answers

What are the three primary ways that HIV is transmitted?

<p>Sexual contact, transmission from infected mother to child, and through blood and blood products</p> Signup and view all the answers

What is the most common route of transmission for HIV worldwide?

<p>Heterosexual transmission</p> Signup and view all the answers

Condom use can reduce the risk of HIV transmission?

<p>True (A)</p> Signup and view all the answers

What percentage of infants born to HIV-positive mothers can become infected during birth?

<p>Up to 40%</p> Signup and view all the answers

What is one way to reduce the risk of HIV transmission from mother to child during birth?

<p>C-section delivery</p> Signup and view all the answers

HIV can be transmitted through breastfeeding.

<p>True (A)</p> Signup and view all the answers

HIV is primarily transmitted through ingestion?

<p>False (B)</p> Signup and view all the answers

HIV is primarily transmitted through touching?

<p>False (B)</p> Signup and view all the answers

Mosquitoes have been shown to transmit HIV?

<p>False (B)</p> Signup and view all the answers

What percentage of people living with HIV are located in Sub-Saharan Africa?

<p>70%</p> Signup and view all the answers

What is the world's highest HIV prevalence?

<p>26%</p> Signup and view all the answers

What percentage of new HIV infections in Sub-Saharan Africa are due to congenital transmission?

<p>15%</p> Signup and view all the answers

What are the three main stages of clinical progression of HIV?

<p>Acute phase, Asymptomatic phase, AIDS (C)</p> Signup and view all the answers

What is the typical duration of the acute stage of HIV infection?

<p>2 to 8 weeks</p> Signup and view all the answers

What process occurs in the acute stage of HIV infection when the body produces antibodies against the virus?

<p>Seroconversion</p> Signup and view all the answers

What is the typical duration of the asymptomatic stage of HIV infection?

<p>10 years</p> Signup and view all the answers

What type of therapy is used to extend the asymptomatic stage of HIV infection?

<p>Antiretroviral therapy (ART)</p> Signup and view all the answers

What term is used for individuals who experience rapid progression through the asymptomatic phase of HIV infection?

<p>&quot;Rapid progressors&quot;</p> Signup and view all the answers

What term is used for individuals who maintain normal CD4 T cell counts and low HIV titers without antiretroviral therapy?

<p>Long-term nonprogressors (LTNPs)</p> Signup and view all the answers

What is the term used to describe a subset of LTNPs who maintain undetectable viral loads?

<p>Elite controllers</p> Signup and view all the answers

What type of immune cells play a key role in controlling HIV, and are often more effective in elite controllers?

<p>Cytotoxic T lymphocytes</p> Signup and view all the answers

What type of infections occur when the CD4 T cell count falls below 500 cells/µL of blood?

<p>Opportunistic infections</p> Signup and view all the answers

What is the CD4 T cell count threshold that marks the progression to AIDS?

<p>200 cells/µL of blood</p> Signup and view all the answers

What is the typical life expectancy of a person diagnosed with AIDS without treatment?

<p>3 years</p> Signup and view all the answers

What is the life expectancy of a person diagnosed with AIDS who acquires an opportunistic infection?

<p>1 year</p> Signup and view all the answers

Which of these options are examples of opportunistic infections? (Select all that apply)

<p>Parasites (A), Fungi (B), Viruses (C), Bacteria (D)</p> Signup and view all the answers

What is the typical time frame for HIV to progress to AIDS without drug treatments?

<p>10 years</p> Signup and view all the answers

The prevalence of HIV continues to rise despite the development of HAART?

<p>True (A)</p> Signup and view all the answers

People living with HIV are more likely to experience neurologic manifestations than those without HIV?

<p>True (A)</p> Signup and view all the answers

What is the term for the protein shell that encapsulates the genetic material of HIV?

<p>Capsid</p> Signup and view all the answers

The capsid of HIV is made of multiple proteins.

<p>False (B)</p> Signup and view all the answers

What type of genetic material is found in HIV?

<p>+ssRNA</p> Signup and view all the answers

Both copies of the +ssRNA genome in HIV are used in reverse transcription.

<p>False (B)</p> Signup and view all the answers

What are the three enzymes found inside the core of HIV?

<p>Reverse transcriptase (RT), Integrase (IN), and Protease (PR)</p> Signup and view all the answers

What is the name of the accessory protein that is involved in transporting cDNA to the nucleus during HIV replication?

<p>Vpr</p> Signup and view all the answers

What is the name of the protein found on the inner surface of the HIV envelope?

<p>Matrix protein (MA)</p> Signup and view all the answers

What are the two glycoproteins found on the surface of the HIV envelope?

<p>Gp120 and gp41</p> Signup and view all the answers

What is another name for gp120?

<p>Surface subunit (SU)</p> Signup and view all the answers

What are the two co-receptors that gp120 interacts with on the surface of host cells?

<p>CCR5 and CXCR4</p> Signup and view all the answers

What type of HIV strain typically infects macrophages and mucosal-associated memory CD4 T cells?

<p>CCR5 tropic or R5 strains</p> Signup and view all the answers

What type of HIV strains are more likely to infect naïve T cells?

<p>CXCR4 tropic or X4 strains</p> Signup and view all the answers

What type of genetic mutation found in the CCR5 gene can potentially make an individual resistant to HIV infection?

<p>CCR5Δ32</p> Signup and view all the answers

The CCR5Δ32 mutation is more common in people of African descent?

<p>False (B)</p> Signup and view all the answers

Individuals homozygous for the CCR5Δ32 mutation are less susceptible to HIV infection than heterozygotes?

<p>True (A)</p> Signup and view all the answers

What type of treatment is often used to treat leukemia?

<p>Myeloablative therapy</p> Signup and view all the answers

What procedure follows myeloablative therapy to reconstitute the immune system of a leukemia patient?

<p>Hematopoietic stem cell transplantation (HSCT)</p> Signup and view all the answers

Why was the "Berlin patient" able to achieve a sustained remission from HIV?

<p>He received bone marrow cells from a donor homozygous for the CCR5Δ32 mutation.</p> Signup and view all the answers

What is the term for the process by which the HIV envelope fuses with the cell membrane?

<p>Penetration</p> Signup and view all the answers

What is the term for shedding the viral capsid after entry into the cell?

<p>Uncoating</p> Signup and view all the answers

What is the term for the process by which the HIV genome is integrated into the host's genome?

<p>Integration</p> Signup and view all the answers

What is the term for the process by which the HIV genome is transcribed and translated into new viral proteins and genetic material?

<p>Transcription and RNA Processing</p> Signup and view all the answers

What is the term for the process by which new viral particles are assembled within the host cell?

<p>Assembly</p> Signup and view all the answers

What is the term for the process by which new HIV particles bud from the host cell membrane?

<p>Release</p> Signup and view all the answers

What is the term for the process by which the viral protease cleaves several sites within Gag and Pol precursors, leading to the formation of mature viral particles?

<p>Maturation</p> Signup and view all the answers

The HIV genome is transcribed by RNA polymerase I?

<p>False (B)</p> Signup and view all the answers

The HIV genome is transcribed into a full-length, unspliced, capped, and polyadenylated mRNA?

<p>True (A)</p> Signup and view all the answers

Transcription of the HIV genome starts within the proviral DNA?

<p>True (A)</p> Signup and view all the answers

What are the two proteins that are crucial for the regulation of HIV gene expression?

<p>Tat and Rev</p> Signup and view all the answers

Tat binds to the viral mRNAs to ensure a full-length transcription process?

<p>True (A)</p> Signup and view all the answers

Rev is responsible for shuttling both spliced and unspliced transcripts from the nucleus to the cytoplasm?

<p>False (B)</p> Signup and view all the answers

What are the three polyproteins that are translated during HIV replication?

<p>Gag precursor, Gag-Pol precursor, and Env precursor</p> Signup and view all the answers

The Gag precursor is cleaved into its individual proteins before the viral particle is released from the cell?

<p>False (B)</p> Signup and view all the answers

The Gag-Pol precursor is translated as a result of a frameshifting event during translation of the Gag precursor?

<p>True (A)</p> Signup and view all the answers

What is the name of the protein that cleaves the Gag precursor into individual proteins?

<p>Protease</p> Signup and view all the answers

What are the four proteins that are produced by the cleavage of the Gag precursor?

<p>Matrix protein (MA), capsid protein (CA), nucleocapsid protein (NC), and p6</p> Signup and view all the answers

The Env precursor is cleaved into gp120 and gp41 in the cytoplasm?

<p>False (B)</p> Signup and view all the answers

What are the six non-essential accessory proteins encoded by HIV?

<p>Vif, Vpr, Vpu, Nef, Tat, and Rev</p> Signup and view all the answers

HIV replication requires the use of host cell transcription factors?

<p>True (A)</p> Signup and view all the answers

What is the name of the region in the HIV genome that contains a viral promoter?

<p>Long terminal repeat (LTR)</p> Signup and view all the answers

The mRNAs for Gag and Gag-Pol are spliced?

<p>False (B)</p> Signup and view all the answers

HIV relies on extensive splicing of viral mRNAs to generate its mature transcripts?

<p>True (A)</p> Signup and view all the answers

HIV vaccines have thus far been highly effective in preventing HIV infection?

<p>False (B)</p> Signup and view all the answers

The clinical course of HIV infection is divided into three stages: ______, ______, and ______.

<p>Acute, Asymptomatic (Clinical Latency), AIDS</p> Signup and view all the answers

The two types of HIV cause clinically distinguishable conditions.

<p>False (B)</p> Signup and view all the answers

Which of the following is NOT a primary route of HIV transmission?

<p>Respiratory secretions (C), Personal contact (E)</p> Signup and view all the answers

What is the name of the first antiretroviral drug approved for HIV infection?

<p>Zidovudine (AZT)</p> Signup and view all the answers

What is the name of the standard HIV treatment that combines several antiviral drugs?

<p>Highly-active antiretroviral therapy (HAART)</p> Signup and view all the answers

A vaccine for HIV/AIDS currently exists.

<p>False (B)</p> Signup and view all the answers

Match the following HIV proteins with their main functions:

<p>Gp120 = Attachment to CD4 and co-receptor Integrase = Integration of viral DNA into host genome Reverse Transcriptase = Conversion of viral RNA to DNA Protease = Cleavage of viral proteins</p> Signup and view all the answers

The HIV-1 group M viruses are the cause of the ______ pandemic.

<p>worldwide</p> Signup and view all the answers

What are the primary sources of SIVs, the simian immunodeficiency viruses that are thought to be the origin of HIV?

<p>Apes and Old World Monkeys</p> Signup and view all the answers

Which of the following is a characteristic of the acute stage of HIV infection?

<p>Seroconversion (A), A high viral load (C), The presence of flu-like symptoms (D)</p> Signup and view all the answers

What is the name of the stage of HIV infection where symptoms are typically absent or limited?

<p>Asymptomatic Phase (Clinical Latency Stage)</p> Signup and view all the answers

Long-term nonprogressors (LTNPs) experience rapid progression to AIDS.

<p>False (B)</p> Signup and view all the answers

Opportunistic infections are infections caused by pathogens that typically do not affect individuals with a healthy immune system.

<p>True (A)</p> Signup and view all the answers

What is the defining characteristic of AIDS?

<p>The development of one or more opportunistic infections, or a CD4 T cell count below 200 cells/µL of blood</p> Signup and view all the answers

Antiretroviral therapy (ART) has no impact on the life expectancy of individuals living with HIV.

<p>False (B)</p> Signup and view all the answers

What is the primary function of the reverse transcriptase enzyme in the HIV replication cycle?

<p>Converting the viral RNA into DNA</p> Signup and view all the answers

The HIV genome is composed of two complete copies of ______.

<p>+ssRNA</p> Signup and view all the answers

The viral capsid plays a role in reverse transcription.

<p>True (A)</p> Signup and view all the answers

What is the name of the protein that coats the viral RNA within the HIV core?

<p>Nucleocapsid protein (NC)</p> Signup and view all the answers

What is the primary receptor that HIV binds to on the surface of host cells?

<p>CD4 (D)</p> Signup and view all the answers

What is the name of the cellular structure that is formed when a dendritic cell carrying HIV comes into contact with a CD4 T cell in the lymph node?

<p>Virological synapse</p> Signup and view all the answers

Dendritic cells act as "______" for HIV.

<p>Trojan horses</p> Signup and view all the answers

What are the two main co-receptors that HIV binds to after attaching to CD4?

<p>CCR5 and CXCR4</p> Signup and view all the answers

CCR5-tropic strains of HIV primarily infect macrophages and a subset of memory CD4 T cells.

<p>True (A)</p> Signup and view all the answers

The 32-base pair deletion in CCR5 known as CCR5A32 leads to a nonfunctional receptor that is unable to be used by any strains of HIV.

<p>False (B)</p> Signup and view all the answers

What is the name of the treatment that uses radiation or chemotherapy to eliminate leukemia cells, but also kills off the immune system cells?

<p>Myeloablative therapy</p> Signup and view all the answers

What is the term for the process of transferring bone marrow stem cells to reconstitute the immune system?

<p>Hematopoietic stem cell transplantation (HSCT)</p> Signup and view all the answers

The "Berlin patient" is the only documented case of a person being cured of HIV.

<p>False (B)</p> Signup and view all the answers

The envelope glycoprotein trimer of HIV mediates the ______ of the virion to the cell surface receptor, CD4.

<p>adsorption</p> Signup and view all the answers

What is the term for the process that releases the viral core, or nucleocapsid, into the cytoplasm of the host cell?

<p>Uncoating</p> Signup and view all the answers

Reverse transcription always occurs outside of the viral capsid.

<p>False (B)</p> Signup and view all the answers

HIV, as a lentivirus, is able to cross nuclear pores without relying on mitosis to break down the nuclear envelope.

<p>True (A)</p> Signup and view all the answers

What is the term for the combination of viral cDNA and proteins that facilitate the entry of the cDNA into the nucleus?

<p>Pre-integration complex (PIC)</p> Signup and view all the answers

The HIV enzyme ______ is responsible for inserting the viral cDNA into the host cell's genome.

<p>Integrase</p> Signup and view all the answers

HIV proviral DNA contains a total of 9 individual proteins.

<p>False (B)</p> Signup and view all the answers

What are the three major genes that are common to most retroviruses?

<p>Gag, Pol, and Env</p> Signup and view all the answers

HIV relies on extensive splicing of its viral mRNAs, resulting in various mature transcripts.

<p>True (A)</p> Signup and view all the answers

What is the function of the Tat protein in HIV replication?

<p>Transactivator of transcription</p> Signup and view all the answers

The Gag precursor is cleaved into MA, CA, NC, and p6 proteins while the virion is still inside the cell.

<p>False (B)</p> Signup and view all the answers

Frame shifting during the translation of the Gag polyprotein always results in the formation of the Gag-Pol precursor.

<p>False (B)</p> Signup and view all the answers

The Env precursor p160 is highly glycosylated in the ______.

<p>rough ER (endoplasmic reticulum)</p> Signup and view all the answers

The release of individual proteins from the Gag and Pol precursors alters the architecture of the capsid and forms an infectious virion.

<p>True (A)</p> Signup and view all the answers

What are the two main challenges that have hindered the development of an effective HIV vaccine?

<ol> <li>Highly variable nature of HIV, 2. Difficulties with traditional vaccine methods</li> </ol> Signup and view all the answers

Candidate HIV vaccines that successfully generated neutralizing antibodies against gp120 demonstrated effectiveness in preventing HIV infections.

<p>False (B)</p> Signup and view all the answers

What is the name of the most promising strategy for developing an HIV vaccine?

<p>Prime-boost strategy</p> Signup and view all the answers

The prime-boost strategy using canarypox and gp120 achieved significant effectiveness in preventing HIV infection in clinical trials.

<p>False (B)</p> Signup and view all the answers

Broadly neutralizing antibodies (bNAbs) that target a wide range of HIV isolates are a promising approach for developing an HIV vaccine.

<p>True (A)</p> Signup and view all the answers

Flashcards

HIV/AIDS discovery date

June 5, 1981, when the CDC reported unusual pneumonia cases in gay men, marking the start of the HIV/AIDS awareness.

AIDS name change

In 1982, the CDC renamed "gay-related immune deficiency" (GRID) to "acquired immune deficiency syndrome" (AIDS) to avoid misclassifying the disease.

HIV Transmission routes

HIV can be transmitted through blood and blood products, sexual contact, and from mother to child.

HIV Taxonomy

HIV belongs to the Retroviridae family, Orthoretrovirinae subfamily, and Lentivirus genus.

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HIV Types

HIV exists in two main types: HIV-1 and HIV-2.

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HIV-1 Groups

HIV-1 is subdivided into groups M, O, N, and P, with Group M being the most prevalent globally.

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HIV-1 Subtypes

Group M is further divided into subtypes (clades), with subtype C being most common worldwide.

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HIV-2 vs. HIV-1

HIV-2 is less easily transmitted, has lower viral loads, and slower progression to AIDS compared to HIV-1.

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Asymptomatic stage

The initial stage of HIV infection, marked by a period of no noticeable symptoms, where HIV replicates and CD4 T cells decline.

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Opportunistic Infections

Infections that occur when the immune system is weakened (as in late-stage HIV).

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AIDS definition

AIDS is diagnosed when a person has opportunistic infections or CD4 counts fall below 200 cells/µL.

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Viral Load

The amount of virus in the body, often used to track HIV infection progression.

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CD4 Count

The number of CD4 T cells in a blood sample, used to monitor immune system health in HIV.

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HIV Replication cycle

A series of steps in which HIV infects a cell, makes copies of itself, and releases new viruses to infect other cells.

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Reverse transcriptase

HIV enzyme that converts viral RNA into DNA.

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Integrase

HIV enzyme that integrates viral DNA into the host cell's DNA.

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Protease

HIV enzyme that cuts proteins into smaller units to create functional viral proteins.

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HIV-1 origin

HIV-1 likely evolved from SIV viruses in chimpanzees.

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HAART/cART

Combination antiretroviral therapy used to treat HIV, targeting multiple stages of viral replication.

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HIV/AIDS Discovery

The first reported cases of a rare pneumonia in young, healthy gay men in 1981 marked the start of the awareness of HIV/AIDS.

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AIDS: A New Name

In 1982, 'gay-related immune deficiency' (GRID) was renamed 'acquired immune deficiency syndrome' (AIDS) to avoid mislabeling and stigma.

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HIV's Family Tree

HIV belongs to the Retroviridae family, specifically the Orthoretrovirinae subfamily, under the Lentivirus genus.

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Two Types of HIV

There are two main types of HIV: HIV-1 and HIV-2, both causing similar symptoms but with differences in transmission and progression.

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Group M: The Pandemic's Cause

HIV-1 Group M is the main cause of the global HIV/AIDS pandemic, with subtypes further diversifying the virus.

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Subtypes: Varied Forms

Within Group M, there are various subtypes (clades) of HIV-1, with subtype C being the most common globally.

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HIV-2: A Slower Pace

HIV-2 is less easily transmitted, has lower viral loads, and progresses to AIDS more slowly compared to HIV-1.

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Phase 1: Asymptomatic

The initial stage of HIV infection is often asymptomatic, meaning people show no or few noticeable symptoms. During this phase, HIV replicates and gradually depletes CD4 T cells.

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CD4 T Cell Decline

The 'silent' phase of HIV infection is marked by a gradual decrease in the number of CD4 T cells, crucial for a healthy immune system.

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Opportunistic Infections: A Sign of Weakness

As the immune system weakens, the body becomes vulnerable to 'opportunistic infections,' caused by pathogens that normally wouldn't cause illness.

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Phase 2: AIDS

AIDS is diagnosed when a person develops one or more opportunistic infections or has a CD4 T cell count below 200 cells/µL, significantly affecting their immune function.

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Viral Load: A Measure of Infection

Viral load refers to the amount of HIV in the body, providing a measure of the infection's progression.

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CD4 Count: Immune Health Gauge

CD4 count, the number of CD4 T cells in a blood sample, indicates the strength of the immune system and is vital for monitoring HIV progression.

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HIV's Replication Cycle: A Step-by-Step Story

HIV's replication cycle involves several critical steps: attachment to a cell, penetration, uncoating, reverse transcription, integration into the host genome, replication, assembly, release, and maturation.

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Reverse Transcriptase: The Viral Script Writer

Reverse transcriptase is an HIV enzyme crucial for converting the viral RNA into DNA, enabling the virus to integrate into the host cell's genome.

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Integrase: The Viral Architect

Integrase is an HIV enzyme that integrates the viral DNA into the host cell's DNA, effectively becoming part of the cell's genetic material.

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Protease: The Viral Sculptor

Protease is an HIV enzyme that cleaves viral proteins into smaller units, enabling them to assemble into functional viral proteins.

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HAART/cART: Combating HIV

Combination antiretroviral therapy (HAART/cART) is a powerful treatment that combines multiple antiviral drugs to target various stages of HIV replication.

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Understanding HIV's Entry Point: CD4

HIV primarily targets cells with CD4 receptors, including helper T cells, macrophages, and dendritic cells, which are crucial for immune function.

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Co-Receptors: Extra Keys for Entry

HIV needs another 'key' called a co-receptor, either CCR5 or CXCR4, in addition to CD4 to gain entry into cells.

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Dendritic Cells: Trojan Horses

Dendritic cells can unknowingly transport HIV to CD4 T cells, serving as 'Trojan horses' for the virus, aiding its spread.

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CCR5 Mutations: Natural Resistance

Some people possess genetic mutations in CCR5, specifically a deletion called CCR532, which can drastically reduce or prevent HIV infection.

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The Berlin Patient: A Medical Miracle

The 'Berlin patient,' treated for leukemia with a bone marrow transplant from a CCR532 donor, became the first known person to be cured of HIV.

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Why No HIV Vaccine?

Despite decades of research, an effective HIV vaccine has eluded scientists due to challenges like the virus's rapid mutation rate, numerous subtypes, and difficulty eliciting a protective immune response.

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Broadly Neutralizing Antibodies: A Rare Hope

Broadly neutralizing antibodies (bNAbs) are a promising area of HIV vaccine research, targeting multiple HIV strains, but they are rare and difficult to elicit.

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HIV: A Scientific Challenge

Researching HIV and finding a vaccine or cure remains one of the greatest scientific challenges of our time, highlighting the virus's complexity and adaptability.

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Study Notes

Chapter 11: Human Immunodeficiency Virus

  • This chapter details the human immunodeficiency virus (HIV)
  • Learning Objectives outline key topics students should grasp post-chapter.
    • Understanding HIV/AIDS history, including discovery and medical advancements
    • HIV taxonomy, groups, and subtypes
    • Origin of HIV-1 and HIV-2
    • Global and US prevalence of HIV/AIDS in various regions, demographics
    • HIV transmission and infection
    • Function of HIV proteins and the viral replication cycle.

History of HIV Infection

  • June 5, 1981: Morbidity and Mortality Weekly Report (MMWR) documented five cases of pneumonia (Pneumocystis jirovecii) in gay men.
  • Additional cases rapidly reported to the CDC.
  • Other illnesses, including Kaposi's sarcoma, emerged in young, previously healthy gay men.
  • 270 cases of severe immunodeficiency reported by the year's end.
  • Subsequently identified as AIDS.
  • 1982: CDC renamed "gay-related immune deficiency" (GRID) to "acquired immune deficiency syndrome" (AIDS).
  • Reports of AIDS in blood transfusion recipients, heterosexual partners of AIDS patients, and hemophiliacs.
  • Hemophiliacs frequently infected via contaminated factor VIII.
  • 1983: CDC documented all major transmission routes
    • Blood and blood products
    • Sexual intercourse, including vaginal and anal sex
    • Congenital transmission
    • Exclusions: respiratory secretions, food/water, air, personal contact
  • Despite these, societal discrimination and violence against infected individuals persist.
  • 1983: Pasteur Institute researchers Françoise Barré-Sinoussi and Luc Montagnier isolated and named a retrovirus (lymphadenopathy-associated virus LAV).
  • Robert Gallo independently identified another retrovirus and named it as HTLV-III.
  • Both viruses found to be the same—human immunodeficiency virus (HIV).
  • 1986: The International Committee on the Taxonomy of Viruses formally names the virus HIV.
  • Slow but steady scientific and societal progress in the decade following.
  • 1985: HIV blood test developed.
  • 1987: First antiretroviral drug, zidovudine (AZT), approved.
  • 1994: Highly active antiretroviral therapy (HAART), a cocktail of antiviral drugs, becomes the standard treatment
    • Also known as combination antiretroviral therapy (CART).
    • Marked a significant reduction in new cases of AIDS.
  • 1996: Number of new AIDS cases decreased significantly for the first time.
  • 2022: (Nearly) 40 years after HIV discovery
    • 1.5 million new infections annually worldwide
    • No HIV/AIDS vaccine yet exists.

Taxonomy and Origins of HIV

  • Two HIV types: HIV-1 and HIV-2

  • Family: Retroviridae

  • Subfamily: Orthoretrovirinae

  • Genera: Lentivirus

  • Species: Human immunodeficiency virus 1 and 2

    • HIV-1 and HIV-2 share similar taxonomic classifications.
    • HIV-2 is less easily transmitted, has lower viral loads and a slower progression to AIDS.
  • HIV-1 further subdivided into distinct groups

    • Group M (main/major): Worldwide pandemic. Group M further divided into subtypes also known as clades (A-K).
    • Group O (outlier): Infrequent in non-African regions, limited to Cameroon and Gabon, and neighboring countries.
    • Group N (non-M, non-O): Similar to group O, though even rarer.
    • Group P (newest group): Found only in Cameroon.
  • HIV-2 further divided into eight distinct groups (A-I).

    • Groups A and B are most prevalent, primarily found in West Africa and Côte d’Ivoire.
    • Groups C-I are rare. No HIV-2 subtypes exist.
  • Originated in chimpanzees.

    • Transmitted to humans.
    • HIV-1 likely originated from SIVcpz (chimpanzees)
    • HIV-2 from sooty mangabey monkeys.
  • Early spread likely through bushmeat hunting in Cameroon and subsequently spread across the DRC.

Epidemiology of HIV/AIDS

  • HIV/AIDS Primarily transmitted via three main methods:

    • Sexual intercourse
    • Infected mother to child: Intrauterine, birth, breast milk. C-section reduces transmission.
    • Blood and blood products: Contaminated needles and medical equipment.
  • Worldwide, heterosexual transmission is the most common mode of HIV transmission.

  • Most new infections occur among stable couples who do not report outside partners and multiple partners.

  • High prevalence in Sub-Saharan Africa, with roughly 70% of infected people residing there. Over half are female.

  • Swaziland maintains the highest prevalence among those aged 15-49.

  • Nearly 690,000 deaths in 2020, globally.

  • New infections fell by 46% from 2000-2020.

  • In 2020, 37.6 million people globally lived with HIV, with 1.5 million new infections.

  • In North America and Western/Central Europe, 2.2 million people lived with HIV in 2020 (half in the US).

    • Incidence peaked at 130,000 new HIV infections in the US in 1984.
    • 2019 saw 36,398 HIV cases diagnosed.
    • Heterosexual contact, male-to-male sexual contact, and IDU accounted for the majority of cases, among others.

Clinical Progression of HIV/AIDS

  • Without treatment, HIV typically progresses to AIDS over a 10-year period.

  • HIV infection has three stages:

    1. Acute stage (2-8 weeks after infection)
      • Symptoms: flu-like illness, fever, swollen lymph nodes, sore throat, muscle aches, headache, fatigue, weight loss.
      • High viral loads; seroconversion—antibodies produced.
    2. Asymptomatic/Clinical Latency Stage(10 years without ART)
      • Slow CD4 T cell depletion.
      • Symptoms are often absent.
      • Rapid progressors: Progression to AIDS from this stage might only take 2-3 years for some.
      • Long-Term Nonprogressors (LTNPs) may maintain normal CD4 counts, but not all.
    3. Acquired Immunodeficiency Syndrome (AIDS)
      • CD4 T-cell count falls below 200 cells/µL of blood.
      • Serious opportunistic infections.
      • AIDS-related complications develop; shorter life expectancies.
  • Other complications include kidney disease and neurologic issues (HIV-associated dementia, encephalitis, and meningitis), due to various contributing factors.

  • HIV continues to evolve, impacting immune response and overall health.

Molecular Virology

  • HIV is an enveloped retrovirus with a cone- or bullet-shaped capsid.
  • Capsid built from a single protein (capsid protein (CA)).
  • Two complete copies of +ssRNA genome.
    • Pseudodiploid—only one copy is used for reverse transcription.
    • +ssRNA—5'-capped and 3' poly(A) tailed, but not infectious.
  • Core contains nucleocapsid protein (NC).
  • Three enzymes: reverse transcriptase (RT), integrase, and protease (PR), along with other accessory proteins.
  • Envelope surrounds the core; Matrix protein (MA) attaches to the inner side.
  • Glycoproteins (gp120 and gp41) are found on the surface of the envelope.
    • gp120 primarily binds to the CD4 receptor and may either bind CCR5 or CXCR4 co-receptors.
    • Important for identifying various HIV-1 strains and HIV infection modes.

Replication of HIV-1

  • Steps of replication:

    • Attachment (to CD4 and co-receptors)
    • Penetration (entry into cells)
    • Uncoating (releasing the genetic material)
    • Reverse transcription (converting RNA genome to DNA)
    • Integration (inserting viral DNA into host DNA)
    • Transcription (making viral mRNA from DNA)
    • RNA processing (modifying viral mRNA)
    • Assembly (creating new viral particles)
    • Release (new viral particles bud from the cell)
  • HIV's proviral DNA contains around 15 individual proteins.

  • Viral RNAs are spliced to generate mature transcripts.

  • HIV's long terminal repeats (LTRs) contain a viral promoter.

  • HIV transcription factors bind to U3, recruiting RNA pol II to proviral DNA.

  • Tat and Rev, regulatory proteins, help in transcription and mRNA processing.

  • Gag, Pol, and Env precursor proteins are first translated as a polyprotein.

  • Cleaved by viral protease into individual functional components.

  • HIV-encoded proteins influence various cellular factors during viral replication.

IN-DEPTH LOOK: Why Doesn't an HIV Vaccine Exist Yet?

  • Difficulty in creating an effective vaccine due to rapid mutation (low fidelity of reverse transcriptase), variation between HIV subtypes, and antibody resistance (high glycosylation).
  • Broadly neutralizing antibodies (bNAbs) are sometimes seen, but require long-term infections for their development
  • Strategies for new vaccines are underway, including a prime-boost approach using adenoviruses, but efficacy remains an issue.

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