Question

There are two known cases of individuals being apparently cured of HIV (Science 332: 784; Lancet HIV 10-Mar-2020). In both cases, an HIV-infected patient developed leukemia and required bone marrow transplant. Each patient received radiation treatments that killed bone marrow and white blood cells throughout his body. Each patient then received a bone marrow transplant, and in each case, the transplant came from a donor carrying a specific deletion in the ccr5 gene. Both patients became extremely ill following the transplant, likely due to leukocytes from the transplanted bone marrow attacking the patient's own cells. After recovery, both patients were able to stop taking anti-retroviral therapy, and they continue to have no detectable HIV in the blood.

Scientists have hypothesized that the most important factor in the apparent cure of these two patients was the fact that the donated bone marrow cells came from an individual with a mutated version of ccr5. Why would this be important?

The donor CD8+ T cells would be especially efficient at identifying and killing HIV-infected cells.

HIV that remained in the patient's body would have difficulty binding to the surface of the donor cells.

HIV that remained in the patient's body would have difficulty synthesizing new viral proteins in the donor cells.

HIV that remained in the patient's body would have difficulty integrating into the genome of the donor cells.

The donor NK cells would be especially efficient at identifying and killing HIV-infected cells.

Radiation treatment kills actively dividing cells, but not all CD4⁺ T cells are actively dividing. In particular, central memory CD4⁺ T cells do not divide very frequently, but in an HIV patient they can harbor the virus. In order for the two patients to be cured of HIV, it would be necessary to get rid of these cells. How could these non-dividing, virally infected CD4+ T cells have been eliminated?

Donor leukocytes recognized them as self via antigens presented on class I MHC

Donor leukocytes recognized them as non-self via antigens presented on class II MHC

They were killed by the radiation treatment like the rest of the immune cells

Donor leukocytes recognized them as self via antigens presented on class II MHC

Donor leukocytes recognized them as non-self via antigens presented on class I MHC

For one of the two patients, the original planned date of his bone marrow transplant had to be delayed because the level of HIV viral particles in his blood suddenly increased very high a week before the planned procedure, even though he was taking anti-retroviral therapy. A rapid increase in virus can sometimes occur in an HIV patient on anti-retroviral therapy. What should a doctor do about this increased viral load?

Do nothing; the problem will resolve on its own

Take the patient off anti-retroviral therapy for a brief period, then re-start the same drugs at the same doses

Increase the dose of the patient's current anti-retroviral drugs

Switch the patient to different anti-retroviral drugs

Answer 1

1. The correct answer is: HIV that remained in the patient's body would have difficulty binding to the surface of the donor cells.

A genetic mutation known as CCR5-delta 32 is responsible for the two types of HIV resistance that exist. CCR5-delta 32 hampers HIV's ability to infiltrate immune cells. The mutation causes the CCR5 co-receptor on the outside of cells to develop smaller than usual and no longer sit outside of the cell. CCR5 co-receptor is like door that allows HIV entrance into the cell. The CCR5-delta 32 mutation in a sense locks "the door" which prevents HIV from entering into the cell. Therefore, CCR5-delta 32 provide resistance to HIV by avoiding the binding of HIV to its receptor.

2. The correct answer is: Donor leukocytes recognized them as non-self via antigens presented on class II MHC.

The selection procedure of T-cells occurs during maturation when some infected or inactivated T-cells are recognised as non-self by immune system and therefore present these as antigens on major histocompatibility complex (MHC). For CD4 cells (T-helper cells), the MHC-II helps in antigen presentation of these cells when they are infected by some pathogens.

3. The correct answer is: Increase the dose of the patient's current anti-retroviral drugs. Antiretroviral drugs should not be stopped when viral load increases in HIV infected patients and therefore be continued or increase for further treatment till bone marrow transplantation occurs.