Slow virus

A slow virus is a virus, or a viruslike agent, etiologically associated with a disease, having a long incubation period of months to years and then a gradual onset of symptoms which progress slowly but irreversibly and terminate in a severe compromised state or, more commonly, death.

A slow virus disease is a disease that, after an extended period of latency, follows a slow, progressive course spanning months to years, frequently involving the central nervous system and ultimately leading to death. Examples include the Visna-Maedi virus, in the genus Lentivirus (family Retroviridae), that causes encephalitis and chronic pneumonitis in sheep, and subacute sclerosing panencephalitis which is apparently caused by the measles virus,^[1] as well as Pagets Disease of Bone (Osteitis Deformans) which is associated with paramyxoviridae, especially RSV and Rubeola (Measles).

Characteristics

Every infectious agent is different, but in general, slow viruses:

• Cause an asymptomatic primary infection
• Have a long incubation period ranging from months to years
• Follow a slow but relentless progressive course leading to death
• Tend to have a genetic predisposition
• Often re-emerge from latency if the host becomes immuno-compromised

Additionally, the immune system seems to plays a limited role, or no role, in protection from these slow viruses. This may be in part because the host has acclimated to the virus, or more likely because the host must be immunocompromised in order for many of these slow virus infections to emerge, so the immune system is at a disadvantage from the start.

Some human infections

Virus	Virus family	Disease	Typical latency	Transmitted by
JC Virus	Polyomavirus	Progressive multifocal leukoencephalopathy	Years to Life^§	Unknown; Contaminated water?
BK Virus	Polyomavirus	BK Nephropathy	Years to life^§	Unknown; respiratory spread/urine?
Rubeola (Measles)	Paramyxovirus	Subacute Sclerosing Panencephalitis	1–10 years	Respiratory droplets
Rubella	Togaviridae	Progressive Rubella Panencephalitis	10–20 years	Respiratory droplets
HIV	Retrovirus	AIDS	5–10 years	Infected blood or other body fluids
HTLV 1	Retrovirus	Adult T-cell Leukemia/Lymphoma	10–30 years	Infected blood or other body fluids
HTLV 2	Retrovirus	Atypical Hairy Cell Leukemia	10–30 years	Infected blood or other body fluids
Rabies Virus	Rhabdoviridae	Rabies	3–12 weeks	Bite of an infected animal

^§JC virus & BK virus only cause disease in immunocompromised patients

Prions: "atypical slow viruses"

Transmissible spongiform encephalopathies (TSEs), including Kuru and Creutzfeldt–Jakob disease of humans, scrapie of sheep, and bovine spongiform encephalopathy (BSE) of cattle, were previously classified as slow virus diseases as well. However, TSEs are more correctly classified as prion diseases. Prions are misfolded proteins that are "infectious" because they can induce misfolding in other previously normal proteins, but they contain no DNA or RNA so they are not viruses.^[2] Before scientists knew the cause of spongeform encephalopathies, they hypothesized that small virus particles, which they termed virions, were to blame. Once it was discovered that prions were the real cause of TSEs and that prions contained no nucleic acid, the term virions was discarded and these particles were renamed prions. A minority of researchers still believe, however, that prion diseases are caused by an as-yet unidentified slow virus, although there is little evidence to support this finding

Prions are so named because they appear to contain only protein.^[3] No evidence of nucleic acid has been found in any prion particle studied. Treatments that destroy protein, like denaturation, destroy prion infectivity, but treatments that destroy nucleic acids, like UV radiation, do not destroy prion infectivity.

The prion protein is known as PrP and is a cell surface glycophosphatidylinositol(GPI)-anchored protein. Its normal function in the body is unknown, though presumably it serves, or served, some purpose because it is coded for by a host gene. The infectious form of PrP has the same amino acid sequence and the same post-translational modifications as the normal form, but it has a different tertiary conformation. The normal PrP contains many alpha-helices, whereas the disease-associated form contains many beta-pleated sheets. It is this conformational change from mostly alpha-helices to mostly beta-pleated sheets that gives the prion its infectious ability.^[4]

The disease-associated form of the prion protein is commonly referred to as PrP^sc because it was first found in scrapie infections in sheep. The diseased form is also occasionally called PrP^res because it is more resistant to protease than the normal, non-disease associated form.

Etiology

In some cases, the etiology of prion diseases is known. Ingestion of a copy of an abnormally folded, infectious PrP can induce a spongiform encephalopathy in the consumer. For example, Kuru is passed through the ritual consumption of brain material in some tribal cultures, and bovine spongiform encephalopathy is thought to have developed from the use of prion-infected sheep protein in cattle feed. However, some cases of spongeform encephalopathies appear to be sporadic, and it is not known in these cases what causes the first prion protein to change its conformation and become infectious. Once one abnormal prion protein exists, however, it can induce the conformational change from predominantly α-helix to predominately β-pleated sheet in neighboring proteins.

Disease presentation

The clinical presentation of prion diseases will vary from patient to patient. However, some general characteristics of prion diseases are listed below.

Prions:

• cause diseases that are confined to the CNS
• have a prolonged incubation period
• follow a slow, progressive, fatal course of disease
• produce a spongiform encephalopathy
• characteristically result in vacuolation of neurons
• can cause formation of fibrillar aggregates, which contain PrP and have amyloid-like characteristics^[5]

See also

• Clinical latency
• Virus latency

References

1. PubMed Health "Subacute Sclerosing Panencephalitis". Retrieved February 10, 2012.
2. Centers for Disease Control and Prevention "Prion Diseases". Retrieved February 10, 2012
3. Prusiner SB. "Prions". Proceedings of the National Academy of Sciences of the United States of America. November 10, 1998; 95(23): 13363–83. Retrieved February 10, 2012.
4. Eghiaian F, et al. "Insight into the PrPC-->PrPSc conversion from the structures of antibody-bound ovine prion scrapie-susceptibility variants." Proceedings of the National Academy of Sciences of the United States of America. July 13, 2004; 101(28): 10254-9. Epub July 6, 2004. Retrieved February 10, 2012.
5. Dr. Margaret Hunt. "Virology Chapter 23 -- Slow Virus Diseases of the Nervous System". Microbiology and Immunology On-line. University of South Carolina School of Medicine. Revised October 2006. Retrieved February 10, 2012.