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Questions and Answers
Questions and Answers
What does the acronym "AIDS" stand for?
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?
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?
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?
What is the name of the fungus that causes the pneumonia described in the first case study?
What type of cancer was also being reported in previously healthy gay men in 1981?
What type of cancer was also being reported in previously healthy gay men in 1981?
What year did the CDC establish the name "Acquired Immune Deficiency Syndrome" (AIDS) for the disease?
What year did the CDC establish the name "Acquired Immune Deficiency Syndrome" (AIDS) for the disease?
What were the main routes of transmission for HIV that the CDC identified in 1983?
What were the main routes of transmission for HIV that the CDC identified in 1983?
HIV can be transmitted through respiratory secretions.
HIV can be transmitted through respiratory secretions.
HIV can be transmitted through sharing food or water.
HIV can be transmitted through sharing food or water.
HIV can be transmitted through air.
HIV can be transmitted through air.
HIV can be transmitted through personal contact.
HIV can be transmitted through personal contact.
What year did Pasteur Institute researchers Françoise Barré-Sinoussi and Luc Montagnier isolate a retrovirus from the lymph node of someone with AIDS?
What year did Pasteur Institute researchers Françoise Barré-Sinoussi and Luc Montagnier isolate a retrovirus from the lymph node of someone with AIDS?
What did Barré-Sinoussi and Montagnier name the retrovirus they isolated?
What did Barré-Sinoussi and Montagnier name the retrovirus they isolated?
What award did Barré-Sinoussi and Montagnier receive for their discovery of the retrovirus?
What award did Barré-Sinoussi and Montagnier receive for their discovery of the retrovirus?
What other retrovirus did Robert Gallo describe in the same issue of Science as Barré-Sinoussi and Montagnier published their finding?
What other retrovirus did Robert Gallo describe in the same issue of Science as Barré-Sinoussi and Montagnier published their finding?
What year did Montagnier and Gallo announce that the two viruses they had discovered were in fact the same virus?
What year did Montagnier and Gallo announce that the two viruses they had discovered were in fact the same virus?
What name was officially given to the retrovirus in 1986?
What name was officially given to the retrovirus in 1986?
What year was the blood test for HIV developed?
What year was the blood test for HIV developed?
What year was the first antiretroviral drug, zidovudine (AZT), approved?
What year was the first antiretroviral drug, zidovudine (AZT), approved?
What year was the AIDS quilt put on display?
What year was the AIDS quilt put on display?
What year did Highly-Active Antiretroviral Therapy (HAART) become the standard treatment for HIV infection?
What year did Highly-Active Antiretroviral Therapy (HAART) become the standard treatment for HIV infection?
What year did the number of new AIDS cases decline for the first time?
What year did the number of new AIDS cases decline for the first time?
What year did the CDC release a public service announcement to address fears about contracting AIDS?
What year did the CDC release a public service announcement to address fears about contracting AIDS?
What year did a vaccine effort using adenovirus to express HIV Gag, Pol, and Nef began?
What year did a vaccine effort using adenovirus to express HIV Gag, Pol, and Nef began?
What is the name of the vaccine strategy that has shown the most promise in combating HIV?
What is the name of the vaccine strategy that has shown the most promise in combating HIV?
What are the two types of HIV?
What are the two types of HIV?
What is the name of the family to which HIV belongs?
What is the name of the family to which HIV belongs?
What is the name of the genera to which HIV belongs?
What is the name of the genera to which HIV belongs?
What group of HIV-1 is responsible for the vast majority of infections worldwide?
What group of HIV-1 is responsible for the vast majority of infections worldwide?
What is the name of the HIV-1 subtype responsible for approximately 50% of infections?
What is the name of the HIV-1 subtype responsible for approximately 50% of infections?
What HIV-1 subtype is most prevalent in Europe and the Americas?
What HIV-1 subtype is most prevalent in Europe and the Americas?
How many distinct groups of HIV-2 have been identified?
How many distinct groups of HIV-2 have been identified?
What are the two groups of HIV-2 that are most prevalent?
What are the two groups of HIV-2 that are most prevalent?
What are the rare groups of HIV-2?
What are the rare groups of HIV-2?
HIV-2 subtypes are more common than HIV-1 subtypes.
HIV-2 subtypes are more common than HIV-1 subtypes.
What type of viruses were the source for the cross-species transmission that led to HIV-1 or HIV-2?
What type of viruses were the source for the cross-species transmission that led to HIV-1 or HIV-2?
What activity is believed to be responsible for transmitting SIVs to humans?
What activity is believed to be responsible for transmitting SIVs to humans?
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?
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?
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?
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?
What is one of the main ways the virus is believed to have spread in Leopoldville?
What is one of the main ways the virus is believed to have spread in Leopoldville?
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?
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?
What are the three primary ways that HIV is transmitted?
What are the three primary ways that HIV is transmitted?
What is the most common route of transmission for HIV worldwide?
What is the most common route of transmission for HIV worldwide?
Condom use can reduce the risk of HIV transmission?
Condom use can reduce the risk of HIV transmission?
What percentage of infants born to HIV-positive mothers can become infected during birth?
What percentage of infants born to HIV-positive mothers can become infected during birth?
What is one way to reduce the risk of HIV transmission from mother to child during birth?
What is one way to reduce the risk of HIV transmission from mother to child during birth?
HIV can be transmitted through breastfeeding.
HIV can be transmitted through breastfeeding.
HIV is primarily transmitted through ingestion?
HIV is primarily transmitted through ingestion?
HIV is primarily transmitted through touching?
HIV is primarily transmitted through touching?
Mosquitoes have been shown to transmit HIV?
Mosquitoes have been shown to transmit HIV?
What percentage of people living with HIV are located in Sub-Saharan Africa?
What percentage of people living with HIV are located in Sub-Saharan Africa?
What is the world's highest HIV prevalence?
What is the world's highest HIV prevalence?
What percentage of new HIV infections in Sub-Saharan Africa are due to congenital transmission?
What percentage of new HIV infections in Sub-Saharan Africa are due to congenital transmission?
What are the three main stages of clinical progression of HIV?
What are the three main stages of clinical progression of HIV?
What is the typical duration of the acute stage of HIV infection?
What is the typical duration of the acute stage of HIV infection?
What process occurs in the acute stage of HIV infection when the body produces antibodies against the virus?
What process occurs in the acute stage of HIV infection when the body produces antibodies against the virus?
What is the typical duration of the asymptomatic stage of HIV infection?
What is the typical duration of the asymptomatic stage of HIV infection?
What type of therapy is used to extend the asymptomatic stage of HIV infection?
What type of therapy is used to extend the asymptomatic stage of HIV infection?
What term is used for individuals who experience rapid progression through the asymptomatic phase of HIV infection?
What term is used for individuals who experience rapid progression through the asymptomatic phase of HIV infection?
What term is used for individuals who maintain normal CD4 T cell counts and low HIV titers without antiretroviral therapy?
What term is used for individuals who maintain normal CD4 T cell counts and low HIV titers without antiretroviral therapy?
What is the term used to describe a subset of LTNPs who maintain undetectable viral loads?
What is the term used to describe a subset of LTNPs who maintain undetectable viral loads?
What type of immune cells play a key role in controlling HIV, and are often more effective in elite controllers?
What type of immune cells play a key role in controlling HIV, and are often more effective in elite controllers?
What type of infections occur when the CD4 T cell count falls below 500 cells/µL of blood?
What type of infections occur when the CD4 T cell count falls below 500 cells/µL of blood?
What is the CD4 T cell count threshold that marks the progression to AIDS?
What is the CD4 T cell count threshold that marks the progression to AIDS?
What is the typical life expectancy of a person diagnosed with AIDS without treatment?
What is the typical life expectancy of a person diagnosed with AIDS without treatment?
What is the life expectancy of a person diagnosed with AIDS who acquires an opportunistic infection?
What is the life expectancy of a person diagnosed with AIDS who acquires an opportunistic infection?
Which of these options are examples of opportunistic infections? (Select all that apply)
Which of these options are examples of opportunistic infections? (Select all that apply)
What is the typical time frame for HIV to progress to AIDS without drug treatments?
What is the typical time frame for HIV to progress to AIDS without drug treatments?
The prevalence of HIV continues to rise despite the development of HAART?
The prevalence of HIV continues to rise despite the development of HAART?
People living with HIV are more likely to experience neurologic manifestations than those without HIV?
People living with HIV are more likely to experience neurologic manifestations than those without HIV?
What is the term for the protein shell that encapsulates the genetic material of HIV?
What is the term for the protein shell that encapsulates the genetic material of HIV?
The capsid of HIV is made of multiple proteins.
The capsid of HIV is made of multiple proteins.
What type of genetic material is found in HIV?
What type of genetic material is found in HIV?
Both copies of the +ssRNA genome in HIV are used in reverse transcription.
Both copies of the +ssRNA genome in HIV are used in reverse transcription.
What are the three enzymes found inside the core of HIV?
What are the three enzymes found inside the core of HIV?
What is the name of the accessory protein that is involved in transporting cDNA to the nucleus during HIV replication?
What is the name of the accessory protein that is involved in transporting cDNA to the nucleus during HIV replication?
What is the name of the protein found on the inner surface of the HIV envelope?
What is the name of the protein found on the inner surface of the HIV envelope?
What are the two glycoproteins found on the surface of the HIV envelope?
What are the two glycoproteins found on the surface of the HIV envelope?
What is another name for gp120?
What is another name for gp120?
What are the two co-receptors that gp120 interacts with on the surface of host cells?
What are the two co-receptors that gp120 interacts with on the surface of host cells?
What type of HIV strain typically infects macrophages and mucosal-associated memory CD4 T cells?
What type of HIV strain typically infects macrophages and mucosal-associated memory CD4 T cells?
What type of HIV strains are more likely to infect naïve T cells?
What type of HIV strains are more likely to infect naïve T cells?
What type of genetic mutation found in the CCR5 gene can potentially make an individual resistant to HIV infection?
What type of genetic mutation found in the CCR5 gene can potentially make an individual resistant to HIV infection?
The CCR5Δ32 mutation is more common in people of African descent?
The CCR5Δ32 mutation is more common in people of African descent?
Individuals homozygous for the CCR5Δ32 mutation are less susceptible to HIV infection than heterozygotes?
Individuals homozygous for the CCR5Δ32 mutation are less susceptible to HIV infection than heterozygotes?
What type of treatment is often used to treat leukemia?
What type of treatment is often used to treat leukemia?
What procedure follows myeloablative therapy to reconstitute the immune system of a leukemia patient?
What procedure follows myeloablative therapy to reconstitute the immune system of a leukemia patient?
Why was the "Berlin patient" able to achieve a sustained remission from HIV?
Why was the "Berlin patient" able to achieve a sustained remission from HIV?
What is the term for the process by which the HIV envelope fuses with the cell membrane?
What is the term for the process by which the HIV envelope fuses with the cell membrane?
What is the term for shedding the viral capsid after entry into the cell?
What is the term for shedding the viral capsid after entry into the cell?
What is the term for the process by which the HIV genome is integrated into the host's genome?
What is the term for the process by which the HIV genome is integrated into the host's genome?
What is the term for the process by which the HIV genome is transcribed and translated into new viral proteins and genetic material?
What is the term for the process by which the HIV genome is transcribed and translated into new viral proteins and genetic material?
What is the term for the process by which new viral particles are assembled within the host cell?
What is the term for the process by which new viral particles are assembled within the host cell?
What is the term for the process by which new HIV particles bud from the host cell membrane?
What is the term for the process by which new HIV particles bud from the host cell membrane?
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?
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?
The HIV genome is transcribed by RNA polymerase I?
The HIV genome is transcribed by RNA polymerase I?
The HIV genome is transcribed into a full-length, unspliced, capped, and polyadenylated mRNA?
The HIV genome is transcribed into a full-length, unspliced, capped, and polyadenylated mRNA?
Transcription of the HIV genome starts within the proviral DNA?
Transcription of the HIV genome starts within the proviral DNA?
What are the two proteins that are crucial for the regulation of HIV gene expression?
What are the two proteins that are crucial for the regulation of HIV gene expression?
Tat binds to the viral mRNAs to ensure a full-length transcription process?
Tat binds to the viral mRNAs to ensure a full-length transcription process?
Rev is responsible for shuttling both spliced and unspliced transcripts from the nucleus to the cytoplasm?
Rev is responsible for shuttling both spliced and unspliced transcripts from the nucleus to the cytoplasm?
What are the three polyproteins that are translated during HIV replication?
What are the three polyproteins that are translated during HIV replication?
The Gag precursor is cleaved into its individual proteins before the viral particle is released from the cell?
The Gag precursor is cleaved into its individual proteins before the viral particle is released from the cell?
The Gag-Pol precursor is translated as a result of a frameshifting event during translation of the Gag precursor?
The Gag-Pol precursor is translated as a result of a frameshifting event during translation of the Gag precursor?
What is the name of the protein that cleaves the Gag precursor into individual proteins?
What is the name of the protein that cleaves the Gag precursor into individual proteins?
What are the four proteins that are produced by the cleavage of the Gag precursor?
What are the four proteins that are produced by the cleavage of the Gag precursor?
The Env precursor is cleaved into gp120 and gp41 in the cytoplasm?
The Env precursor is cleaved into gp120 and gp41 in the cytoplasm?
What are the six non-essential accessory proteins encoded by HIV?
What are the six non-essential accessory proteins encoded by HIV?
HIV replication requires the use of host cell transcription factors?
HIV replication requires the use of host cell transcription factors?
What is the name of the region in the HIV genome that contains a viral promoter?
What is the name of the region in the HIV genome that contains a viral promoter?
The mRNAs for Gag and Gag-Pol are spliced?
The mRNAs for Gag and Gag-Pol are spliced?
HIV relies on extensive splicing of viral mRNAs to generate its mature transcripts?
HIV relies on extensive splicing of viral mRNAs to generate its mature transcripts?
HIV vaccines have thus far been highly effective in preventing HIV infection?
HIV vaccines have thus far been highly effective in preventing HIV infection?
The clinical course of HIV infection is divided into three stages: ______, ______, and ______.
The clinical course of HIV infection is divided into three stages: ______, ______, and ______.
The two types of HIV cause clinically distinguishable conditions.
The two types of HIV cause clinically distinguishable conditions.
Which of the following is NOT a primary route of HIV transmission?
Which of the following is NOT a primary route of HIV transmission?
What is the name of the first antiretroviral drug approved for HIV infection?
What is the name of the first antiretroviral drug approved for HIV infection?
What is the name of the standard HIV treatment that combines several antiviral drugs?
What is the name of the standard HIV treatment that combines several antiviral drugs?
A vaccine for HIV/AIDS currently exists.
A vaccine for HIV/AIDS currently exists.
Match the following HIV proteins with their main functions:
Match the following HIV proteins with their main functions:
The HIV-1 group M viruses are the cause of the ______ pandemic.
The HIV-1 group M viruses are the cause of the ______ pandemic.
What are the primary sources of SIVs, the simian immunodeficiency viruses that are thought to be the origin of HIV?
What are the primary sources of SIVs, the simian immunodeficiency viruses that are thought to be the origin of HIV?
Which of the following is a characteristic of the acute stage of HIV infection?
Which of the following is a characteristic of the acute stage of HIV infection?
What is the name of the stage of HIV infection where symptoms are typically absent or limited?
What is the name of the stage of HIV infection where symptoms are typically absent or limited?
Long-term nonprogressors (LTNPs) experience rapid progression to AIDS.
Long-term nonprogressors (LTNPs) experience rapid progression to AIDS.
Opportunistic infections are infections caused by pathogens that typically do not affect individuals with a healthy immune system.
Opportunistic infections are infections caused by pathogens that typically do not affect individuals with a healthy immune system.
What is the defining characteristic of AIDS?
What is the defining characteristic of AIDS?
Antiretroviral therapy (ART) has no impact on the life expectancy of individuals living with HIV.
Antiretroviral therapy (ART) has no impact on the life expectancy of individuals living with HIV.
What is the primary function of the reverse transcriptase enzyme in the HIV replication cycle?
What is the primary function of the reverse transcriptase enzyme in the HIV replication cycle?
The HIV genome is composed of two complete copies of ______.
The HIV genome is composed of two complete copies of ______.
The viral capsid plays a role in reverse transcription.
The viral capsid plays a role in reverse transcription.
What is the name of the protein that coats the viral RNA within the HIV core?
What is the name of the protein that coats the viral RNA within the HIV core?
What is the primary receptor that HIV binds to on the surface of host cells?
What is the primary receptor that HIV binds to on the surface of host cells?
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?
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?
Dendritic cells act as "______" for HIV.
Dendritic cells act as "______" for HIV.
What are the two main co-receptors that HIV binds to after attaching to CD4?
What are the two main co-receptors that HIV binds to after attaching to CD4?
CCR5-tropic strains of HIV primarily infect macrophages and a subset of memory CD4 T cells.
CCR5-tropic strains of HIV primarily infect macrophages and a subset of memory CD4 T cells.
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.
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.
What is the name of the treatment that uses radiation or chemotherapy to eliminate leukemia cells, but also kills off the immune system cells?
What is the name of the treatment that uses radiation or chemotherapy to eliminate leukemia cells, but also kills off the immune system cells?
What is the term for the process of transferring bone marrow stem cells to reconstitute the immune system?
What is the term for the process of transferring bone marrow stem cells to reconstitute the immune system?
The "Berlin patient" is the only documented case of a person being cured of HIV.
The "Berlin patient" is the only documented case of a person being cured of HIV.
The envelope glycoprotein trimer of HIV mediates the ______ of the virion to the cell surface receptor, CD4.
The envelope glycoprotein trimer of HIV mediates the ______ of the virion to the cell surface receptor, CD4.
What is the term for the process that releases the viral core, or nucleocapsid, into the cytoplasm of the host cell?
What is the term for the process that releases the viral core, or nucleocapsid, into the cytoplasm of the host cell?
Reverse transcription always occurs outside of the viral capsid.
Reverse transcription always occurs outside of the viral capsid.
HIV, as a lentivirus, is able to cross nuclear pores without relying on mitosis to break down the nuclear envelope.
HIV, as a lentivirus, is able to cross nuclear pores without relying on mitosis to break down the nuclear envelope.
What is the term for the combination of viral cDNA and proteins that facilitate the entry of the cDNA into the nucleus?
What is the term for the combination of viral cDNA and proteins that facilitate the entry of the cDNA into the nucleus?
The HIV enzyme ______ is responsible for inserting the viral cDNA into the host cell's genome.
The HIV enzyme ______ is responsible for inserting the viral cDNA into the host cell's genome.
HIV proviral DNA contains a total of 9 individual proteins.
HIV proviral DNA contains a total of 9 individual proteins.
What are the three major genes that are common to most retroviruses?
What are the three major genes that are common to most retroviruses?
HIV relies on extensive splicing of its viral mRNAs, resulting in various mature transcripts.
HIV relies on extensive splicing of its viral mRNAs, resulting in various mature transcripts.
What is the function of the Tat protein in HIV replication?
What is the function of the Tat protein in HIV replication?
The Gag precursor is cleaved into MA, CA, NC, and p6 proteins while the virion is still inside the cell.
The Gag precursor is cleaved into MA, CA, NC, and p6 proteins while the virion is still inside the cell.
Frame shifting during the translation of the Gag polyprotein always results in the formation of the Gag-Pol precursor.
Frame shifting during the translation of the Gag polyprotein always results in the formation of the Gag-Pol precursor.
The Env precursor p160 is highly glycosylated in the ______.
The Env precursor p160 is highly glycosylated in the ______.
The release of individual proteins from the Gag and Pol precursors alters the architecture of the capsid and forms an infectious virion.
The release of individual proteins from the Gag and Pol precursors alters the architecture of the capsid and forms an infectious virion.
What are the two main challenges that have hindered the development of an effective HIV vaccine?
What are the two main challenges that have hindered the development of an effective HIV vaccine?
Candidate HIV vaccines that successfully generated neutralizing antibodies against gp120 demonstrated effectiveness in preventing HIV infections.
Candidate HIV vaccines that successfully generated neutralizing antibodies against gp120 demonstrated effectiveness in preventing HIV infections.
What is the name of the most promising strategy for developing an HIV vaccine?
What is the name of the most promising strategy for developing an HIV vaccine?
The prime-boost strategy using canarypox and gp120 achieved significant effectiveness in preventing HIV infection in clinical trials.
The prime-boost strategy using canarypox and gp120 achieved significant effectiveness in preventing HIV infection in clinical trials.
Broadly neutralizing antibodies (bNAbs) that target a wide range of HIV isolates are a promising approach for developing an HIV vaccine.
Broadly neutralizing antibodies (bNAbs) that target a wide range of HIV isolates are a promising approach for developing an HIV vaccine.
Questions and Answers
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Flashcards
Flashcards
HIV/AIDS discovery date
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
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 Transmission routes
HIV can be transmitted through blood and blood products, sexual contact, and from mother to child.
HIV Taxonomy
HIV Taxonomy
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HIV Types
HIV Types
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HIV-1 Groups
HIV-1 Groups
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HIV-1 Subtypes
HIV-1 Subtypes
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HIV-2 vs. HIV-1
HIV-2 vs. HIV-1
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Asymptomatic stage
Asymptomatic stage
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Opportunistic Infections
Opportunistic Infections
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AIDS definition
AIDS definition
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Viral Load
Viral Load
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CD4 Count
CD4 Count
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HIV Replication cycle
HIV Replication cycle
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Reverse transcriptase
Reverse transcriptase
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Integrase
Integrase
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Protease
Protease
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HIV-1 origin
HIV-1 origin
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HAART/cART
HAART/cART
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HIV/AIDS Discovery
HIV/AIDS Discovery
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AIDS: A New Name
AIDS: A New Name
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HIV's Family Tree
HIV's Family Tree
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Two Types of HIV
Two Types of HIV
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Group M: The Pandemic's Cause
Group M: The Pandemic's Cause
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Subtypes: Varied Forms
Subtypes: Varied Forms
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HIV-2: A Slower Pace
HIV-2: A Slower Pace
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Phase 1: Asymptomatic
Phase 1: Asymptomatic
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CD4 T Cell Decline
CD4 T Cell Decline
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Opportunistic Infections: A Sign of Weakness
Opportunistic Infections: A Sign of Weakness
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Phase 2: AIDS
Phase 2: AIDS
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Viral Load: A Measure of Infection
Viral Load: A Measure of Infection
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CD4 Count: Immune Health Gauge
CD4 Count: Immune Health Gauge
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HIV's Replication Cycle: A Step-by-Step Story
HIV's Replication Cycle: A Step-by-Step Story
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Reverse Transcriptase: The Viral Script Writer
Reverse Transcriptase: The Viral Script Writer
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Integrase: The Viral Architect
Integrase: The Viral Architect
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Protease: The Viral Sculptor
Protease: The Viral Sculptor
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HAART/cART: Combating HIV
HAART/cART: Combating HIV
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Understanding HIV's Entry Point: CD4
Understanding HIV's Entry Point: CD4
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Co-Receptors: Extra Keys for Entry
Co-Receptors: Extra Keys for Entry
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Dendritic Cells: Trojan Horses
Dendritic Cells: Trojan Horses
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CCR5 Mutations: Natural Resistance
CCR5 Mutations: Natural Resistance
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The Berlin Patient: A Medical Miracle
The Berlin Patient: A Medical Miracle
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Why No HIV Vaccine?
Why No HIV Vaccine?
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Broadly Neutralizing Antibodies: A Rare Hope
Broadly Neutralizing Antibodies: A Rare Hope
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HIV: A Scientific Challenge
HIV: A Scientific Challenge
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Study Notes
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.
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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.
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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.
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Originated in chimpanzees.
- Transmitted to humans.
- HIV-1 likely originated from SIVcpz (chimpanzees)
- HIV-2 from sooty mangabey monkeys.
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Early spread likely through bushmeat hunting in Cameroon and subsequently spread across the DRC.
Epidemiology of HIV/AIDS
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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.
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Worldwide, heterosexual transmission is the most common mode of HIV transmission.
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Most new infections occur among stable couples who do not report outside partners and multiple partners.
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High prevalence in Sub-Saharan Africa, with roughly 70% of infected people residing there. Over half are female.
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Swaziland maintains the highest prevalence among those aged 15-49.
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Nearly 690,000 deaths in 2020, globally.
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New infections fell by 46% from 2000-2020.
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In 2020, 37.6 million people globally lived with HIV, with 1.5 million new infections.
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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
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Without treatment, HIV typically progresses to AIDS over a 10-year period.
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HIV infection has three stages:
- 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.
- 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.
- 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.
- Acute stage (2-8 weeks after infection)
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Other complications include kidney disease and neurologic issues (HIV-associated dementia, encephalitis, and meningitis), due to various contributing factors.
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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
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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)
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HIV's proviral DNA contains around 15 individual proteins.
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Viral RNAs are spliced to generate mature transcripts.
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HIV's long terminal repeats (LTRs) contain a viral promoter.
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HIV transcription factors bind to U3, recruiting RNA pol II to proviral DNA.
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Tat and Rev, regulatory proteins, help in transcription and mRNA processing.
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Gag, Pol, and Env precursor proteins are first translated as a polyprotein.
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Cleaved by viral protease into individual functional components.
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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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