BK virus

BK virus
Other names: BK virus infection[1]
Top:(Hypothetical) model for BKV pathogenesis that include infection of GVU cells[2], the mechanisms underlying BK virus latency and reactivation are not fully understood[3] Bottom:Map of Polyomaviridae genome(BKV genome is a closed circular, double-stranded DNA molecule)[4]
Specialty	Infectious disease
Symptoms	No symptoms, or may have trouble urinating[5]
Risk factors	Organ transplant, immune system[6]
Diagnostic method	Blood and Urine test[7]
Differential diagnosis	Cytomegalovirus infection, Herpes infection[8]
Treatment	Lower does of anti-rejection drug(and cidofovir)[9]

BK virus (BK virus infection), also known as Human polyomavirus 1^[10], is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. BK virus is an abbreviation of the name of the first patient, from whom the virus was isolated in 1971 .^[11][12][13]

Treatment for Bk virus infection includes antiviral medications, such as cidofovir and leflunomide(among other)^[14]

Signs and symptoms

The BK virus rarely causes disease but is typically associated with patients who have had a kidney transplant; many people who are infected with this virus are asymptomatic. If symptoms do appear, they tend to be mild: respiratory infection or fever. These are known as primary BK infections. Although without any clinical symptoms, footprints of BK virus have been detected in specimens from females affected by spontaneous abortion.^[15] Serum antibodies against BK virus have also been found in spontaneous abortion affected women as well as in women who underwent voluntary interruption of pregnancy.^[16]

The virus then disseminates to the kidneys and urinary tract where it persists for the life of the individual. It is thought that a high percentage of the population contains a latent form of this virus, which remains latent until the body undergoes some form of immunosuppression. Typically, this is in the setting of kidney transplantation or multi-organ transplantation. Presentation in these immunocompromised individuals is much more severe. Clinical manifestations include renal dysfunction, and an abnormal urinalysis revealing renal tubular cells and inflammatory cells.^[17][18]

Cause

Similarly to JC virus and SV40, BK virus has a small, non-enveloped, icosahedral capsid with a diameter of 45–50 nm.^[19] The capsid is made up of viral proteins VP1, VP2, and VP3. The capsid proteins have T=7 arrangement. The icosahedral structure contains 72 pentamers of the major capsid protein VP1, 360 molecules in total. Each penton is bound the minor capsid proteins VP2 or VP3 on the inside of the virus while VP1 protein shell is on the outside.^[20]

Transmission

It is not known how this virus is transmitted, except that it spreads from person to person, and not from an animal source. It has been suggested that this virus may be transmitted through respiratory fluids or urine, since infected individuals periodically excrete virus in the urine. A survey of 400 healthy blood donors was reported as showing that 82% were positive for IgG against BK virus.^[21]

Risk factors

In some renal transplant patients, the necessary use of immunosuppressive drugs has the side-effect of allowing the virus to replicate within the graft, a disease called BK nephropathy.^[22]

From 1–10% of renal transplant patients progress to BK virus associated nephropathy (BKVAN) and up to 80% of these patients lose their grafts. The onset of nephritis can occur as early as several days post-transplant to as late as 5 years.^[6]

It is also associated with ureteral stenosis and interstitial nephritis. In bone marrow transplant recipients it is notable as a cause for hemorrhagic cystitis.^[23][18][24]

BK viremia load > 185 000 copies/ml at the time of first positive BKV diagnosis - to be the strongest predictor for BKVAN (97% specificity and 75% sensitivity). In addition the BKV peak viral loads in blood reaching 223 000 copies/ml at any time was found to be predictive for BKVAN (91% specificity and 88% sensitivity) .^[25]

Diagnosis

This virus can be diagnosed by a BKV blood test or a urine test for decoy cells, in addition to carrying out a biopsy in the kidneys. PCR techniques are often carried out to identify the virus.^[26]

• 
  Cytology of a polyomavirus infected cell, using Papanicolaou stain. The high nuclear to cytoplasmic ratio makes it resemble cancer (thus the name "decoy cell") but the inclusion body reveals its viral pathophysiology.
• 
  Micrograph showing a polyomavirus infected cell — large (blue) cell below-center-left. Urine cytology specimen.

Differential diagnosis

As to the DDx we find the following should be considered:^[27][8]

• JCPyV
• Human adenovirus
• CMV
• Herpes simplex virus

Treatment

The cornerstone of therapy is reduction in immunosuppression. A recent surge in BKVAN correlates with use of potent immunosuppressant drugs, such as tacrolimus and mycophenolate mofetil (MMF). Studies have not shown any correlation between BKVAN and a single immunosuppressive agent but rather the overall immunosuppressive load.^[28][7]

• Most common methods:^[7][28][6]

1. Withdrawal of MMF or tacrolimus
2. Replacement of tacrolimus by cyclosporine
3. Overall reduction of immunosuppressive load

Other therapeutic options include Leflunomide, Cidofovir, IVIG, and the fluoroquinolones. Leflunomide, a pyrimidine synthesis inhibitor is now generally accepted as the second treatment option behind reduction of immunosuppression.^[29]

Leflunomide in BKVAN

The rationale behind using leflunomide in BKVAN comes from its combined immunosuppressive and antiviral properties. Two studies consisting of 26 and 17 patients who developed BKVAN on a three-drug regimen of tacrolimus, MMF, and steroids had their MMF replaced with leflunomide 20–60 mg daily. 84 and 88% of patients, respectively had clearance or a progressive reduction in viral load and a stabilization or improvement of graft function. In a study conducted by Teschner et al. in 2009, 12/13 patients who had their MMF exchanged with leflunomide cleared the virus by 109 days.^{[30] [31][29][32]}

Epidemiology

In terms of the prevalence BKPyV is rather common and has been detected in a significant proportion of population. Studies have shown that a large percentage of adults have antibodies to BKPyV, indicating past infection^[33]

History

The BK virus was first isolated in 1971 from the urine of a renal transplant patient, initials B.K. The BK virus is similar to another virus called the JC virus (JCV), since their genomes share 75% sequence similarity. Both of these viruses can be identified and differentiated from each other by carrying out serological tests using specific antibodies or by using a PCR-based genotyping approach.^[34][35]

See also

• Decoy cells
• Low-dose naltrexone

References

Further reading

• "BK virus". Am. J. Transplant. 4 (Suppl 10): 89–91. November 2004. doi:10.1111/j.1600-6135.2004.00730.x. PMID 15504220. S2CID 30891138.
• Blanckaert K, De Vriese AS (December 2006). "Current recommendations for diagnosis and management of polyoma BK virus nephropathy in renal transplant recipients". Nephrol. Dial. Transplant. 21 (12): 3364–7. doi:10.1093/ndt/gfl404. PMID 16998219.

External links

• Overview of the BK virus
• MicrobiologyBytes: Polyomaviruses