BK virus (Hemorrhagic cystitis)

BK virus, or BKV, is named after the initials of the patient in whom the virus was first identified. BK virus typically infects the urinary system of immunocompromised individuals, or those with a weakened immune system, especially those receiving immunosuppressive medications following organ transplants.

Major clinical manifestations of BKV infection include hemorrhagic cystitis, which is inflammation of the urinary bladder associated with bloody urine, in bone marrow transplant recipients; ureteral stenosis, or narrowing, and nephropathy in kidney transplant recipients.

BK virus belongs to the polyomavirus family along with the JC virus. These contain a circular double-stranded DNA genome which is surrounded by an icosahedral capsid, which is a spherical protein shell made up of 20 equilateral triangular faces. They are also called non-enveloped viruses since the capsid isn’t covered by a lipid membrane.

It turns out that the vast majority of the population is infected with BK virus during their childhood. The virus is thought to be transmitted from person to person through respiratory droplets when someone coughs or sneezes and by ingesting contaminated food and water.

Once inside, the virus moves through the bloodstream and eventually reaches the kidneys, specifically the renal tubular epithelial cells, where it starts to replicate. But, the cytotoxic CD8+ T cells of our immune system keep the virus in check by killing any cell that has replicating BK virus inside it. However, the sneaky little viruses are not eliminated, but instead they hit the snooze button, and go into a latent phase within the kidney epithelial cells. In other words, they’re not dividing or causing disease.

Most people with a healthy immune system are able to keep BK virus in the latent phase in the kidney epithelial cells for their entire life. But things can change if the immune system gets weaker. This can happen for various reasons, like an HIV-infected individual who loses T cells, or individuals taking immunosuppressive medications like tacrolimus. Tacrolimus is a medication primarily used to reduce the immune response after organ transplantation to prevent transplant rejection. BK virus infection is especially common in kidney and bone marrow transplant recipients.

In immunocompromised individuals, T-cells are affected, and without them, the BK virus in the epithelial cells starts multiplying once again, which results in tubular cell death by lysis, or the breakdown of the cell membrane, releasing the virus into the interstitial tissue. This elicits an inflammatory response from the host. Namely, white blood cells like macrophages found in the affected tissue release inflammatory mediators like histamine and cytokines. This makes blood vessels in the infected area dilate and become more permeable, allowing more leukocytes and fluid to enter local tissue. The end result are the four cardinal signs of inflammation: heat, pain, redness, and swelling.