Polyoma Viruses

Question 1

Objectives:

1. Recall the oncogenic nature of polyoma viruses in non-permissive hosts
2. Recall the epidemiology, pathogenesis, and diagnosis of BK and JC virus infections
3. Describe the relationship of JC virus to progressive multifocal leukoencephalopathy

Question 2

Describe the polyoma virus

Answer 2

Belongs to the papovaviridae family (subfamily papilloma, polyoma)- vacuolating virus SV40

Question 3

What is the structure of the polyoma virus

Answer 3

circular double-strand DNA genome (5-8 kilobase pairs) packaged around histone with a non-enveloped icosahedral capsid

Question 4

How does polyoma transmission/replication occur?

Answer 4

In permissive cells, replication and assembly of progeny occurs in nucleus and virions are released by cell lysis

In non-permissive cells, infection leads to transformation of cells and the polyoma virus genome integrates into host chromosome

Question 5

How does transformation of non-permissive cells with polyoma virus work?

Answer 5

There are two transcriptional classes of genes: Early genes encode three T antigens, needed to initiate DNA replication and responsible for transformation (analogous to E6 and E7 of papilloma virus)

ii. small T and large T antigens are necessary to immortalize cells
iii. small T and middle T antigen are needed to transform cells
2. late genes encode the structural proteins of the virion

Question 6

What are the two known polyoma human viruses?

Answer 6

BK and JC virus (Both BK and JC viruses can produce tumors in hamsters and mice)

Question 7

More about BK and JC viruses

Answer 7

DNA from both can transform many non-human cell lines

Question 8

BK and JC viruses are ubiquitous (>80% adult seropositivity) but not oncogenic in humans (permissive host)

Answer 8

1. 50% of US children are seropositive for BK virus by 3-4 years of age
2. 50% of US children are seropositive for JC virus by 10-14 years of age
3. infection in healthy children is most often subclinical

Question 9

How do BK and JC viral infection progress?

Answer 9

There is an initial replication at the site of infection (respiratory or GI tract) followed by viremia and passage to kidney, lung, or brain

NOTE: These viruses persistently infect the kidney

Question 10

BK or JC virus infection is only a problem in:

Answer 10

immunodeficient hosts: AIDS and transplant patients

Question 11

BK virus can be isolated from the urine of AIDS patients, but little disease

Question 12

JC virus is the etiologic agent of:

Answer 12

progressive multifocal leukoencephalopathy (PML)

Question 13

What is PML?

Answer 13

A progressive demyelinating disease of the CNS probably due to reactivated JC virus which makes its way to the CNS and infects and lyses oligodendrocytes

Question 14

What are the symptoms of PML?

Answer 14

clumsiness, progressive weakness or speech problems in a matter of weeks

NOTE: 2-5% of AIDS patients will develop PML

Question 15

How is JC virus infection diagnosed?

Answer 15

1. PCR amplification of JC virus DNA from CSF or brain biopsy
2. detection of white matter lesions by MRI

Question 16

What is the prognosis of PML?

Answer 16

There is no virus-specific tx for PML

In transplant patients, you can alter the immunosuppression, but still 80% fatality rate within 6 months. Similarly, you can adjust HAART tx in AIDs pts but mortality is still 50%