3.2.4 HIV AS AN EXAMPLE OF A HUMAN DISEASE CAUSED BY A VIRUS

Q: When the new HIV viruses are released from the T cell (see part c), the T cell bursts/lyses and is destroyed. This destruction of T cells is very dangerous and could eventually cause the death of someone infected with HIV. Explain why. (2 MARKS)

- (Eventually, there are) not enough/no T cells to activate B cells / lead to antibody production / activate the immune system OR the death/destruction of T cells weakens the immune system; - (This leads to the infected) person unable to fight / more prone to (opportunistic) infections/cancer/diseases; - (Such as) named example of infection/cancer/disease e.g. TB / pneumonia;

Q: The graph shows changes in the number of T-cells and HIV particles in the blood of a person following infection. Explain why the number of HIV particles in the blood rises during the first few months after infection (2 MARKS)

- (HIV is) invading cells which make new viruses; - Cells release viruses into blood:

EQ: The genetic material in HIV mutates at a very high rate. Mutations in the genes coding for integrase and reverse transcriptase are very common. Many of the antiviral drugs used for treatment of HIV-infected patients are inhibitors of either integrase or reverse transcriptase. Treatment with a single drug often results in the development of resistance in the virus and the patient becomes ill. Treatment with two drugs at the same time, each drug targeting a different enzyme, does not result in resistance. The patient stays healthy. Suggest an explanation for the different effects of treatment with a single antiviral drug and treatment with two drugs at the same time. (4 MARKS)

- A mutation in the 1st drug causes a change in the structure of a protein / enzyme / integrase / reverse transcriptase ; - (Mutant) ernzyme is now effective in the presence of the (single) drug ; - So virus can replicate and infect other (CD4 helper T-) cells as 1st drug cannot stop replication; - With 2 drugs: unlikely to have >1 mutation in one virus ; - So at least one enzyme is inhibited and virus cannot replicate ;

Describe the general structure of a virus.

- Acellular → not made of or able to be divided into cells - Non-living → unable to exist / reproduce without a host cell - Genetic material can either be DNA or RNA

Why are antibiotics ineffective against viruses?

- Antibiotics can't enter human cells - but viruses exists in its host cell (they are acellular), so difficult to destroy hem without harming host cells - Antibiotics can also act on metabolic processes, viruses don't have own metabolic reactions e.g. ribosomes (use the host cell's) which antibiotics target - If we did them... act as a selection pressure + gene mutation = resistant strain of bacteria via natural selection → reducing effectiveness of antibiotics and waste of money - Antibiotics like penicillin for bacteria inhibit certain enzymes required for synthesis and assembly of the cross-linkages in bacterial cell walls. This weakens the walls making them unable to withstand pressure, and therefore burst. However viruses have a protein coat rather than a murein cell wall so the don't have sites where antibiotics can work.

Draw and describe the general structure of HIV.

- Core: genetic material (RNA) and the enzyme reverse transcriptase, which are needed for viral replication - Nucleocapsid surrounds the RNA and protects it - Capsid: outer protein coat surrounds nucleocapsid, enclosing the genetic material and the enzymes transcriptase, integrase and protease and gives added protection to the genome - Envelope: extra outer layer made out of membrane taken from the host's cell membrane (outer protective coat), and containing glycoproteins - Protein attachments: on the exterior of the envelope (glycoproteins) to enable the virus to attach to the host's helper T cell

Q: Describe how new viruses are produced after HIV has infected a T cell. (3 MARKS)

- DNA copy made of viral RNA - Inserted into host DNA / chromosomes - Uses viral DNA to make viral proteins / particles - Makes viral RNA - Host cell makes new viruses - Budding odd / wrapped in cell membrane

Describe the latency period (in terms of HIV)

- During initial infection period, HIV replicates rapidly - After this, HIV replication drops to a lower level - latency period - Infected person won't experience any symptoms

What are the symptoms of the intial (acute) stage of HIV?

- Flu-like symptoms - After this period, HIV replication drops to a lower level. This is the latency period. During the latency period (which can last for years) the infected person wont experience any symptoms.

Q: The graph shows changes in the number of T-cells and HIV particles in the blood of a person following infection. This person developed a large number of infections about 9 years after he first became infected with HIV. Using information from the graph, explain why. (4 MARKS)

- HIV destroys T cells; - More (free) viruses produced leads to fall in T-cells; - (So fewer) T-cells activate B-cells/memory cells; - Reduced/no antibody production; - Immune system not working properly/inability to fight infection; - Opportunistic infections;

Q: Figure 2 shows some of the changes that take place in the blood after infection by HIV. Use Figure 2 and your own knowledge to explain how infection with HIV eventually leads to the development of AIDS. (4 MARKS)

- HIV infects and replicates inside T helper cells AND destroys / reduces function of T helper cells; - Amount of virus in blood increases SO more T helper cells become infected (a spiral of T cell decline become unavoidable); - T helper cells can no longer produce chemicals that increase the activity of T killer cells, so infected cells are not destroyed; - T helper cells can no longer produce chemicals that activate B cells, So antibody production decreases;

Q: HIV infects human cells by binding to a cell surface receptor called CD4. This binding causes a shape change in the viral surface glycoproteins, enabling the virus to enter the host cell. A new treatment for HIV involves a monoclonal antibody called Ibalizumab. A trial looking at the efficacy of Ibalizumab investigated its impact on CD4 cell (also known as helper T cell) count after 25 weeks of treatment. The results are shown in Figure 3 and include the standard deviations for each group of patients. State and explain what can be concluded about the efficacy of Ibalizumab from the results shown in Figure 3.

- Ibalizumab is effective in reducing HIV infection AS CD4/helper T cell count increases after treatment; - Ibalizumab is effective at improving the immune response of HIV patients AS their CD4/helper T cells are able to activate antibody production / killer T cell activity; - The mean change from baseline CD4 cell count after treatment does not differ significantly between patients with <50 CD4 cells / µl and with >50 CD4 cells / µl AS the standard deviations overlap;

Q: HIV infects human cells by binding to a cell surface receptor called CD4. This binding causes a shape change in the viral surface glycoproteins, enabling the virus to enter the host cell. A new treatment for HIV involves a monoclonal antibody called Ibalizumab, the action of which is shown in Figure 2 below. Suggest how lbalizumab works as a treatment for HIV. (3 MARKS)

- Ibalizumab structure is complementary to that of the human CD4 receptor SO it binds to it; - This prevents the HIV glycoprotein from binding to CD4 SO it cannot enter the host cell OR this prevents the shape change in the virus glycoproteins SO it cannot enter the cell; - If HIV cannot enter host cells then it cannot reproduce, so the infection cannot continue OR the host immune system can destroy infected cells at a faster rate than new cells become infected;

Q: Antiviral drugs have been developed to treat patients infected with Human Immunodeficiency Virus (HIV). Some antiviral drugs used to treat patients infected with HIV are inhibitors of enzymes found within HIV. Suggest how these antiviral drugs would work in the treatment of patients infected with HIV. (3 MARKS)

- Idea that drugs would prevent viral replication OR idea that T (helper) cells / lymphocytes will not be killed / burst / destroyed(by virus particles leaving cell) - Idea of inhibition of reverse transcriptase - Idea that (viral) DNA could not be made from the (viral) RNA OR idea that (viral) DNA cannot integrate into (host) DNA / genome

Describe how HIV causes the symptoms of AIDS (acquired immunodeficiency syndrome).

- Infect and kills helper T cells (host cell) as it multiplies rapidly (low TH cell count) - T helper cells then can't stimulate cytotoxic T cells, B cells and phagocytes → impaired immune response - Eg B plasma cells cant secrete antibodies for agglutination and destruction of pathogens by phagocytosis (no antibodies produced) - Without TH cells, immune cells die - Immune system deteriorates → develop AIDS (acquired immune deficiency syndrome) - More susceptible to infections - Opportunistic disease that would cause minor problems in healthy immune system are deadly (opportunistic infections) e.g. pneumonia, tuberculosis

Describe what protease inhibitors do.

- Inhibit enzymes responsible for completing the modification of the proteins that are incorporated into new virus particles. - Prevents modification / cleave / hydrolysis of proteins - Prevents synthesis of viral proteins

What are the symptoms of AIDS?

- Initial symptoms of AIDS include minor infections of mucous membranes (e.g. the inside of the nose, ears and genitals), and recurring respiratory infections. - As AIDS progresses the number of immune system cells decreases further. Patients become susceptible to more serious infections including chronic diarrhea, severe bacterial infections and tuberculosis. - During the late stages of AIDS patients have a very low number of immune system cells and can develop a range of serious infections such as toxoplasmosis of the brain (a parasite infection) and candidiasis of the respiratory system (fungal infection). It's these serious infections that kill AIDS patients, not HIV itself.

EQ: HIV contains the enzymes integrase and reverse transcriptase. A human CD4 helper T-cell contains the enzyme DNA polymerase. Describe the function of each of these enzymes in the infection of a CD4 helper T-cell with HIV. (3 MARKS)

- Integrase: Joins (double-stranded) DNA into host cell chromosome/into host DNA ; - Reverse transcriptase: Makes (single-stranded) DNA complement of RNA ; - DNA polymerase: Makes double-stranded (c)DNA from single stranded DNA ;

Q: What is an antigen? (2 MARKS)

- Molecule/part of molecule/protein/glycoprotein; - Stimulates immune response;

Q: The destruction of T-cells by HIV leads to the death of an infected person. Explain how. (2 MARKS)

- Not enough / no T-cells to activate B-cells/ to activate immune system - Person unable to fight / more prone to opportunistic infections / cancer

Q: The diagram shows the structure of human immunodeficiency virus (HIV). State how the genetic material in HIV differs from the genetic material in the bacterium mycobacterium tuberculosis that causes TB. (2 MARKS)

- RNA in HIV and DNA in bacterium OR plasmids - Circular in bacterium and linear in HIV

Q: Fig. 1.1 shows a simplified diagram of the structure of the infective agent that causes the condition known as AIDS. The infective agent that causes AIDS takes control of the T lymphocytes of the host. Using the information in Fig. 1.1, suggest why the infective agent is able to 'take control' once it has entered the T lymphocytes. (4 MARKS)

- Reverse transcriptase in host nucleus - Viral DNA inserted in host chromosome / DNA - Idea of: viral DNA / mRNA produced / transcribed - To code for / make / translate viral proteins

EQ: New viruses are produced after HIV has infected a T cell. Describe how viral enzymes are involved in this process. (3 MARKS)

- Reverse transcriptase makes cDNA/complementary DNA from the (viral) RNA (template); - Reverse transcriptase makes a second strand of DNA using cDNA as template; - Integrase inserts (new/viral) DNA into host DNA / chromosomes; - Protease cuts/cleaves the polypeptide/polyprotein to form several functional proteins (required to produce new viruses)

Q: Describe how HIV is replicated after it has entered a human cell. (4 MARKS)

- Reverse transcriptase; - Enzyme uses (HIV) RNA to make DNA (copy); - DNA inserted to (host) cell's DNA/chromosome; - DNA used to make viral HIV RNA (copies); - And HIV viral capsid proteins / enzymes; - Made at (host) ribosomes; - Assembly of new virus particles; - Budding off from membrane (of host cell);

How can transmission of HIV be avoided?

- Safe and protected sex - Avoiding blood contact

Q: The diagram in Figure 1 shows a human immunodeficiency virus (HIV). Name structure C in Figure 1 and state its function in this virus. (2 MARKS)

- Structure = RNA (molecule); - Function = (RNA) carries genetic information;

Q: Anti-viral drugs have been developed to treat patients infected with HIV. The diagram shows the structure of HIV. Explain how the structure G enables HIV to infect human cells. (3 MARKS)

- Structure G is a glycoprotein / gp120 used for attachment (attachment protein) - Attaches / binds to receptors - On T helper cells / lymphocytes

Q: Figure 2 shows three stages of the process during which HIV infects Helper T cells. Describe the events that take place in order for step 2 in Figure 2 to progress on to step 3. (2 MARKS)

- The host cell uses the viral genetic material to transcribe/translate/synthesise viral proteins; - The viral proteins can then be assembled into new virus particles;

Q: Figure 2 shows some of the changes that take place in the blood after infection by HIV. Use Figure 2 to explain why those infected with HIV experience an asymptomatic period (period without symptoms) between 2-10 years. (2 MARKS)

- The numbers of virus particles / amount of HIV RNA in the blood is reduced SO few cells become infected (during this time); - Numbers of T cells AND antibodies remain high, SO any new infected cells are destroyed;

Q: Myeloid leukaemia is a type of cancer. Monoclonal antibodies are used in treating it. A monoclonal antibody will bind to an antigen on a myeloid leukaemia cell. It will not bind to other types of cell. Explain why this antibody binds only to an antigen on a myeloid leukaemia cell. (2 MARKS)

- These antigens/antibodies have complementary/particular shape; [Reject: Active site] - Allow fitting/binding with (relevant) antibody/antigen;

Q: Ebola is a disease caused by a virus. The Ebola virus has a glycoprotein on its surface which binds to a specific receptor protein in the cell surface membranes of human cells. When it binds to this receptor protein, the virus can enter the cell. Some people do not produce this receptor protein. These people may become infected with the Ebola virus but do not develop the disease. Explain why they don't develop the disease. (3 MARKS)

- Virus cant bind to receptor / can enter cells - So can't be replicated / multiply (cant reproduce) - So doesn't damage cells / tissues and cause symptoms (no toxins released)

Q: Explain how viruses cause damage to cells. (3 MARKS)

- uses / breaks up / digests host nuclear / genetic material (allow references made to DNA /RNA instead of nuclear /genetic); - virus DNA / genetic material inserted into hosts DNA / chromosome / genetic material; - host cells amino acids are used to synthesize viral proteins; - cell lysis; - by enzyme (produced by expressing a virus gene); - toxin production;

Q: Hepatitis A is a disease caused by a virus, which can permanently damage the liver and other organs, such as the pancreas. The hepatitis A virus is an RNA virus usually transmitted by drinking water contaminated with the faeces of infected people. It exists as a single immunological type. Heating the virus to 100 °C for five minutes inactivates its infectivity. 1. Suggest why the virus causes damage only to some types of human cell. (1 MARK) 2. Suggest why effective vaccines cannot be produced using hepatitis A viruses that have been heated to 100 °C. (1 MARK) 3. Explain what is meant by hepatitis A virus existing as a single immunological type. (2 MARKS)

1. (shape of) virus fits / binds / attaches to receptors / proteins in the cell membrane (of host); 2. antigen / protein structure / shape changed by heat; 3. - one type of antigen / protein / shape / one strain of virus; - same immune response generated;

EQ: When HIV infects a human cell, the following events occur. - A single-stranded length of HIV DNA is made. - The human cell then makes a complementary strand to the HIV DNA. The complementary strand is made in the same way as a new complementary strand is made during semi-conservative replication of human DNA. Describe how the complementary strand of HIV DNA is made. (3 MARKS)

1. (Complementary) nucleotides/bases pair OR A to T and C to G; 2. DNA polymerase; 3. Nucleotides join together (to form new strand)/phosphodiester bonds form;

EQ: Read the following passage. Azidothymidine (AZT) is a drug used to treat people infected with human immunodeficiency virus (HIV). It inhibits the enzyme that synthesises DNA from HIV RNA. This does not destroy HIV in the body but stops or slows the development of AIDS. In the past, some people who took AZT on its own eventually developed AIDS. Some of the HIV in their bodies had become resistant to AZT. To prevent this from happening, people infected with HIV are now treated with highly active antiretroviral therapy (HAART). This involves taking AZT with other anti-HIV drugs at the same time. AZT is taken in low doses. This is because people who took high doses over long periods of time suffered muscle wastage. It was found that high doses of AZT inhibit replication of mitochondria. Use information from the passage and your own knowledge to answer the questions. Suggest why high doses of AZT lead to muscle wastage (lines 10-11). (2 MARKS)

1. (Fewer mitochondria so) less (aerobic) respiration; 2. (Muscles receive) less ATP (so waste);

Q: The human immunodeficiency virus (HIV) leads to the development of acquired immunodeficiency syndrome (AIDS). Eventually, people with AIDS die because they are unable to produce an immune response to pathogens. Scientists are trying to develop an effective vaccine to protect people against HIV. There are three main problems. HIV rapidly enters host cells. HIV causes the death of T cells that activate B cells. HIV shows a lot of antigenic variability. Scientists have experimented with different types of vaccine for HIV. One type contains HIV in an inactivated form. A second type contains attenuated HIV which replicates in the body but does not kill host cells. A third type uses a different, non-pathogenic virus to carry genetic information from HIV into the person's cells. This makes the person's cells produce HIV proteins. So far, these types of vaccine have not been considered safe to use in a mass vaccination programme. Explain why HIV rapidly entering host cells means that a vaccine might not be effective against HIV. (2 MARKS)

1. (HIV enters cells) before antibodies can bind to / destroy it; 2. Antibodies cannot enter cells (to destroy HIV) / stay in blood; OR 3. (Enters cells) before (secondary) immune response caused / before memory cells have time to respond; 4. So no antibodies present (to attack HIV); OR 5. Vaccine taken up too quickly to cause immune response; 6. So no antibodies / memory cells formed;

EQ: Drugs can be used for treating HIV. Suggest how drugs such as integrase inhibitors (INIs) and protease inhibitors (PIs) may prevent the onset of AIDS. (3 MARKS)

1. (Integrase inhibitors / INIs) prevent HIV/viral DNA from being integrated into cell's DNA; 2. (Protease inhibitors / PIs) prevent HIV/viral proteins being produced (from host cell proteins) / prevents modification of new HIV/viral proteins; 3. Inhibits/prevents the replication of HIV / prevents new virus particles from being assembled;

EQ: HIV attaches to a specific protein receptor on helper T cells. A low percentage of people have a mutation of the CCR5 gene which codes for this protein receptor. This mutation results in a non-functional protein receptor. People with the CCR5 mutation show a greater resistance to developing AIDS. Explain why. (2 MARKS)

1. (Receptor) is not complementary OR (HIV) cannot bind/attach and enter/infect (helper) T cell; 2. No replication (of virus) OR No destruction of (helper) T cell;

Q: The human immunodeficiency virus (HIV) leads to the development of acquired immunodeficiency syndrome (AIDS). Eventually, people with AIDS die because they are unable to produce an immune response to pathogens. Scientists are trying to develop an effective vaccine to protect people against HIV. There are three main problems. HIV rapidly enters host cells. HIV causes the death of T cells that activate B cells. HIV shows a lot of antigenic variability. Scientists have experimented with different types of vaccine for HIV. One type contains HIV in an inactivated form. A second type contains attenuated HIV which replicates in the body but does not kill host cells. A third type uses a different, non-pathogenic virus to carry genetic information from HIV into the person's cells. This makes the person's cells produce HIV proteins. So far, these types of vaccine have not been considered safe to use in a mass vaccination programme. Explain why HIV showing a lot of antigenic variability means that a vaccine might not be effective against HIV. (2 MARKS)

1. Antigen (on HIV) changes; 2. (Specific) antibody / receptor no longer binds to (new) antigen; OR 3. Many different strains of HIV / many antigens present on HIV; 4. Not possible to make a vaccine for all antigens / vaccine may not stimulate an antibody for a particular antigen;

EQ: The graph below shows typical progress of an HIV infection. Clinical wellness and viral load are in arbitrary units. Clinical wellness is a measure of AIDS symptoms. Explain how HIV reduces the clinical wellness value during stages 3 and 4 in the graph. (3 MARKS)

1. Replication of HIV/virus/particles/increased viral load / destroys/infects/reduces number of T (helper) cells/CD4 cells; 2. T cells/CD4 cells required for immune response/stimulate B cells; 3. AIDS is a series of (opportunistic) diseases caused by immune system not working/insufficient T cells/CD4 cells;

Why is HIV called a retrovirus?

Because the HIV enzyme reverse transcriptase copies the viral RNA and synthesises it into a DNA copy

Q: Figure 1 below shows the structure of the human immunodeficiency virus (HIV). Suggest the functions of the following HIV component: Glycoprotein. (1 MARK)

Binds to complementary cell surface receptors to gain entry to a host cell;

Describe what attachment & entry inhibitors do.

Block attachment points for the HIV viral protein onto helper T cell. Some bind to proteins on virus whereas others bind to receptors on the cell

How can HIV be treated?

Can be treated using antiretroviral therapy; a range of different drugs, each different type of drug targets a different stage in the replication & spread of HIV, eg: - Reverse transcriptase inhibitors - Integrase inhibitors - Protease inhibitors - Attachment & entry inhibitors (usually not included in mark schemes so stick with the first 3)

Q: The human immunodeficiency virus (HIV) leads to the development of acquired immunodeficiency syndrome (AIDS). Eventually, people with AIDS die because they are unable to produce an immune response to pathogens. Scientists are trying to develop an effective vaccine to protect people against HIV. There are three main problems. HIV rapidly enters host cells. HIV causes the death of T cells that activate B cells. HIV shows a lot of antigenic variability. Scientists have experimented with different types of vaccine for HIV. One type contains HIV in an inactivated form. A second type contains attenuated HIV which replicates in the body but does not kill host cells. A third type uses a different, non-pathogenic virus to carry genetic information from HIV into the person's cells. This makes the person's cells produce HIV proteins. So far, these types of vaccine have not been considered safe to use in a mass vaccination programme. Suggest why they have not been considered safe. (3 MARKS)

E.g. 1. Inactive virus may become active / viral transformation; 2. Attenuated virus might become harmful; 3. Non-pathogenic virus may mutate and harm cells; 4. Genetic information / protein (from HIV) may harm cells; 5. People (may) become / test HIV positive after vaccine used; 6. This may affect their work / life;

Q: Figure 2 shows some of the changes that take place in the blood after infection by HIV. Use information in Figure 2 to explain the changes in HIV RNA copies in the plasma during the first 14 weeks after infection. (3 MARKS)

HIV RNA plasma copies increase during the first 8 weeks because: - HIV infects host cells and uses their protein synthesis mechanisms to produce more copies of itself / produce more copies of its genetic material/RNA; HIV RNA plasma copies decrease between 8-14 weeks because: - An increase in killer T cells leads to the destruction of infected cells; - An increase in HIV antibodies leads to phagocytosis of infected cells;

TIP!!

HIV attachment proteins are foreign antigens that can be recognised by the immune system. During replication, the virus can change parts of the structure of its attachment proteins. This is antigenic variation and it helps HIV evade destruction by the immune system.

IMPORTANT!

HIV doesn't kill individuals directly, by infecting the immune system it prevents it from functioning properly, therefore making the immune system weaker and more likely to be severely affected by other pathogens, leading to fatality. It's these serious infections that kill AIDS patients, not HIV itself.

What type of disease is HIV, and how can it be transmitted?

HIV is a sexually transmitted infection (STI), it can pass from one individual to another through: - Semen - Vaginal fluid - Breastmilk - From mother to child across the placenta - Blood - Glycoproteins - Capsid

TIP!!!!!

HIV testing, based on HIV antibody detection, before a baby is 18 months old can be inaccurate. This is because the baby of an HIV-positive mother may have some HIV antibodies in their blood (passed over from their mother in the womb) regardless of whether or not they're infected.

Draw the structure of a virus (Not, HIV, just in general)

Look at image.

EQ: Table 1 shows features of a bacterium and the human immunodeficiency virus (HIV) particle. Complete Table 1 by putting a tick (X) where a feature is present. (2 MARKS)

Look at image.

Q: Read the following passage. Herpes simplex virus (HSV) infects nerve cells in the face, including some near the lips. Like many other viruses, HSV can remain inactive inside the body for years. When HSV becomes active, it causes cold sores around the mouth. Human cells infected with a virus may undergo programmed cell death. While HSV is inactive inside the body, only one of its genes is transcribed. This gene is the latency-associated transcript (LAT) gene that prevents programmed cell death of an infected nerve cell. Scientists have found that transcription of the LAT gene produces a microRNA. This microRNA binds to some of the nerve cell's own mRNA molecules. These mRNA molecules are involved in programmed cell death of nerve cells. The scientists concluded that production of this microRNA allows HSV to remain in the body for years. Suggest one advantage of programmed cell death (line 4). (1 MARK)

Prevents replication of virus.

Why does HIV convert its RNA to DNA?

So it can integrate into the host cell DNA so the host cell generates new HIV particles

TIP!!!

The HIV attachment proteins are also called envelope proteins.

Q: Figure 2 shows three stages of the process during which HIV infects Helper T cells. State how the events shown in Figure 2 lead to the development of AIDS. (2 MARKS)

The events in Figure 2 lead to AIDS because... - Helper T cells are destroyed; AND Any one of the following: - There will be no release of cytokines/chemical signals; - B lymphocytes can't be activated; - Plasma cells can't develop; - No antibodies are produced; - Phagocyte activity won't be increased; - The new viruses can go on to infect and destroy more helper T cells;

TIP!

The length of time that people survive with AIDS varies a lot. Factors that affect progression of HIV to AIDS and survival time with AIDS include existing infections, the strain of HIV they're infected with, age and access to healthcare.

What is prophylaxis?

The use of drugs to prevent disease

Q: Describe the function of the surface proteins on HIV. (1 MARK)

To attach to (host/human) cells/receptors/CD4 cells;

TIP!!!!

Try not to confuse the terms HIV and AIDS. Many people often use them interchangeably when they actually mean different things. - HIV is a virus - AIDS is the disease caused by HIV

Q: The graph shows changes in the number of T-cells and HIV particles in the blood of a person following infection. Explain why the number of HIV particles in the blood remains low between 1 and 7 years after infection. (1 MARK)

Virus remains dormant/exists as provirus/exists as DNA in host DNA;

Q: The human immunodeficiency virus (HIV) leads to the development of acquired immunodeficiency syndrome (AIDS). Eventually, people with AIDS die because they are unable to produce an immune response to pathogens. Scientists are trying to develop an effective vaccine to protect people against HIV. There are three main problems. HIV rapidly enters host cells. HIV causes the death of T cells that activate B cells. HIV shows a lot of antigenic variability. Scientists have experimented with different types of vaccine for HIV. One type contains HIV in an inactivated form. A second type contains attenuated HIV which replicates in the body but does not kill host cells. A third type uses a different, non-pathogenic virus to carry genetic information from HIV into the person's cells. This makes the person's cells produce HIV proteins. So far, these types of vaccine have not been considered safe to use in a mass vaccination programme. People with AIDS die because they are unable to produce an immune response to pathogens (lines 2-4). Explain why this leads to death.

1. Infected by/susceptible to (other) pathogen(s)/named disease caused by a pathogen (from environment); 2. Pathogen(s) reproduce/cause disease (in host); 3. Damage cells/tissues/organs; 4. Release toxins;

EQ: HIV attaches to a specific protein receptor on helper T cells. A low percentage of people have a mutation of the CCR5 gene which codes for this protein receptor. This mutation results in a non-functional protein receptor. The frequency of the CCR5 mutation is highest in Europe. Scientists have collected data on the history and number of HIV infections in Europe. Using these data, scientists have concluded that the high frequency of the CCR5 mutation is not due to natural selection in response to HIV. Suggest two reasons why scientists reached this conclusion. (2 MARKS)

1. Low/lower exposure to HIV (in Europe) OR Low/lower number of HIV AIDS (infections/cases); 2. (HIV) has only been present for a short time period OR (HIV relatively) recently evolved; 3. Mutation/CCR5 has been around for many years; 4. Mutation/CCR5 is advantageous (for something else);

Q: Read the following passage. Herpes simplex virus (HSV) infects nerve cells in the face, including some near the lips. Like many other viruses, HSV can remain inactive inside the body for years. When HSV becomes active, it causes cold sores around the mouth. Human cells infected with a virus may undergo programmed cell death. While HSV is inactive inside the body, only one of its genes is transcribed. This gene is the latency-associated transcript (LAT) gene that prevents programmed cell death of an infected nerve cell. Scientists have found that transcription of the LAT gene produces a microRNA. This microRNA binds to some of the nerve cell's own mRNA molecules. These mRNA molecules are involved in programmed cell death of nerve cells. The scientists concluded that production of this microRNA allows HSV to remain in the body for years. HSV can remain inactive inside the body for years (lines 2-3). Explain why this virus can be described as inactive. (2 MARKS)

1. No more (nerve) cells infected / no more cold sores form; 2. (Because) virus is not replicating.

Q: Read the following passage. Herpes simplex virus (HSV) infects nerve cells in the face, including some near the lips. Like many other viruses, HSV can remain inactive inside the body for years. When HSV becomes active, it causes cold sores around the mouth. Human cells infected with a virus may undergo programmed cell death. While HSV is inactive inside the body, only one of its genes is transcribed. This gene is the latency-associated transcript (LAT) gene that prevents programmed cell death of an infected nerve cell. Scientists have found that transcription of the LAT gene produces a microRNA. This microRNA binds to some of the nerve cell's own mRNA molecules. These mRNA molecules are involved in programmed cell death of nerve cells. The scientists concluded that production of this microRNA allows HSV to remain in the body for years. HSV infects nerve cells in the face (line 1). Explain why it infects only nerve cells. (3 MARKS)

1. Outside of virus has antigens / proteins; 2. With complementary shape to receptor / protein in membrane of cells; 3. (Receptor / protein) found only on membrane of nerve cells.

EQ: The graph below shows typical progress of an HIV infection. Clinical wellness and viral load are in arbitrary units. Describe the effect of HIV on the CD4 cell count through stages 1-2. Use the data in the graph. (2 MARKS)

1. Overall pattern: Initial decrease then increase/return to normal followed by decrease; 2. Suitable values from graph: Peak 530-550, trough 400;

EQ: Read the following passage. Azidothymidine (AZT) is a drug used to treat people infected with human immunodeficiency virus (HIV). It inhibits the enzyme that synthesises DNA from HIV RNA. This does not destroy HIV in the body but stops or slows the development of AIDS. In the past, some people who took AZT on its own eventually developed AIDS. Some of the HIV in their bodies had become resistant to AZT. To prevent this from happening, people infected with HIV are now treated with highly active antiretroviral therapy (HAART). This involves taking AZT with other anti-HIV drugs at the same time. AZT is taken in low doses. This is because people who took high doses over long periods of time suffered muscle wastage. It was found that high doses of AZT inhibit replication of mitochondria. Use information from the passage and your own knowledge to answer the questions. Suggest and explain why AZT does not destroy HIV in the body but stops or slows the development of AIDS (lines 3-4). (4 MARKS)

1. Person (infected with HIV) has HIV DNA (in their DNA); 2. New HIV (particles) still made; 3. (AZT) inhibits reverse transcriptase; 4. (AZT) stops these (new HIV particles) from forming new HIV DNA; OR Slows / stops replication of HIV; 5. Stops destruction of more / newly infected T cells; 6. So immune system continues to work (and AIDS does not develop);

Q: Cauliflower mosaic virus (CaMV) infects plants in the Brassica family including cauliflower and oilseed rape. The leaves of oilseed rape plants infected with CAMV turn yellow. This kills the plant. Most aphids do not have wings and remain on the same plant. Sometimes females with wings are produced. The graph shows the relationship between the mean number of female aphids with wings and the viral load per plant. 1. What does the graph show about the number of aphids with wings? (1 MARK) 2. Suggest how the relationship shown in the graph benefits the aphids. (1 MARK)

1. Positive correlation between increased viral load and number of aphids with wings; 2. (As viral load increases oilseed rape plant more likely to die) more aphids with wings so can move to new plant;

EQ: Read the following passage. Azidothymidine (AZT) is a drug used to treat people infected with human immunodeficiency virus (HIV). It inhibits the enzyme that synthesises DNA from HIV RNA. This does not destroy HIV in the body but stops or slows the development of AIDS. In the past, some people who took AZT on its own eventually developed AIDS. Some of the HIV in their bodies had become resistant to AZT. To prevent this from happening, people infected with HIV are now treated with highly active antiretroviral therapy (HAART). This involves taking AZT with other anti-HIV drugs at the same time. AZT is taken in low doses. This is because people who took high doses over long periods of time suffered muscle wastage. It was found that high doses of AZT inhibit replication of mitochondria. Use information from the passage and your own knowledge to answer the questions. Suggest and explain two advantages of using HAART (lines 7-9). (4 MARKS)

1. Slows / stops the development of AIDS; 2. Because HIV resistant to AZT is damaged / destroyed / prevented from replicating (by other drugs); OR 3. AZT continues to work as a drug; 4. Because HAART prevents the spread of AZT-resistant HIV to rest of the human population; OR 5. No new HIV particles made; 6. Because HAART might interfere with viral protein synthesis;

Describe the replication of HIV in T helper cells.

Enters blood stream and circulates around body: 1. HIV infects T helper cells (host cell) - HIV attachment protein (GP120) attached to a receptor on the host (CD4) → helper T-cell membrane 2. Virus lipid envelope fuses with cell surface membrane and capsid released into the cell which uncoats, releasing RNA, reverse transcriptase & integrase into cytoplasm 3. Viral DNA is made from viral RNA - Reverse transcriptase produces a complementary viral DNA strand from viral RNA template - Double stranded DNA is transcribed from this (DNA polymerase) 4. Viral DNA enters nucleus via nuclear pore & integrated into host cell's DNA (by viral enzyme integrase) 5. This remains latent for a time in host cell until activated 6. Host cells (T helper cells) make more copies of the virus genetic material as they duplicate 7. Upon activation, viral DNA hijacks the cell, forcing host cell enzymes to transcribe the viral DNA to make viral mRNA. This viral mRNA then hijacks the host cells ribosomes and force it to only make viral proteins. Without making its own proteins, the host cell wont survive. 8. → viral proteins, enzymes and RNA assembled to make a new virus 9. New virus reforms capsid and bud from host cell (taking some of cell surface membrane as envelope) 10. Upon release, each new viral particle infects more T helper cells to replicate more HIV 11. Eventually kills helper T cells 12. Most host cells are infected and process repeat

Q: Read the following passage. Herpes simplex virus (HSV) infects nerve cells in the face, including some near the lips. Like many other viruses, HSV can remain inactive inside the body for years. When HSV becomes active, it causes cold sores around the mouth. Human cells infected with a virus may undergo programmed cell death. While HSV is inactive inside the body, only one of its genes is transcribed. This gene is the latency-associated transcript (LAT) gene that prevents programmed cell death of an infected nerve cell. Scientists have found that transcription of the LAT gene produces a microRNA. This microRNA binds to some of the nerve cell's own mRNA molecules. These mRNA molecules are involved in programmed cell death of nerve cells. The scientists concluded that production of this microRNA allows HSV to remain in the body for years. The scientists concluded that production of this microRNA allows HSV to remain in the body for years (lines 10-12). Explain how this microRNA allows HSV to remain in the body for years. (4 MARKS)

MicroRNA binds to cell's mRNA (no mark) 1. (Binds) by specific base pairing; 2. (So) prevents mRNA being read by ribosomes; 3. (So) prevents translation / production of proteins; 4. (Proteins) that cause cell death.

Describe what integrase inhibitors do.

Once reverse transcriptase has synthesised a DNA copy of the viral RNA, this copy must become a part of the genomic DNA. This is called integration. Integrase inhibitors prevent HIV from integrating its genome into the host genome, which also ultimately prevents it from replicating by acting on the enzyme responsible for this process.

Describe what reverse transcriptase inhibitors do.

Prevent HIV converting its RNA to DNA. Two types: - Non-nucleoside inhibitors are non-competitive inhibitors, binding to reverse transcriptase at a region away from active site. - Nucleoside inhibitors act as alternative nucleotides in the synthesis of viral DNA copy. When they are incorporated into the viral DNA copy, the polynucleotide chain is terminated - Prevents RNA being transcribed to (single-stranded) DNA - Prevents synthesis of viral proteins