6. viruses viroids prions end

• Persistent Viral Infections

In the 1950’s, these were originally called slow viral infections. Persistent viral infections is a better term 

• Three basic categories of persistent viral infections: 

• Continuously infectious form such as Hepatitis B 

• Low or partial infectivity such as adenoviruses in tonsils and/or adenoids 

• Completely non-infectious periods (latent infections) but with occasional flare-ups or reactivation of viral activity (patent infections) 

Latent Viral Infections 

• Virus remains in equilibrium with the host and may not cause disease for long time periods, maybe years 

• Herpes simple virus is one example 

-HSV-1 causes cold sores 

-HSV-2 once called the genital strain, is the sexually transmitted variant of HSV-1 

-Colonization sites are less clearly distinct  

Herpes simplx viral infections

• Herpes simplex viral infections 

• Cold sore virus picked up from saliva exchange or contact with an actual cold sore vesicle 

• Cold sore lesion may heal but virus is still present 

• Becomes latent in sensory neurons 

• May become re-activated by several triggers: 

-Sensory stimuli arriving in the neuron from skin areas responding to sunlight 

-Certain fevers during other infections (fever blisters) 

-Hormonal influences, (pregnancy, stress)

• Red dots show the location of infection 

• Black dots show the locations of latency 

• Varicella-Zoster virus 

May also exist in a latent form 

• Contact through inhalation of respiratory secretion droplets and saliva or by direct contact with active skin lesions 

• Initial contact - varicella  (chickenpox) 

• Latency of the VZV is also in nervous tissue 

• Reactivation causes “shingles” 

sneezing

Sneezing is a common cause of aerosolization. 

• Large droplets may travel 1-2 M before falling out of the air column. 

• Smaller droplets may stay suspended for several hours.

Common manifestations of Varicella-zoster virus initial infections. Bunch of pictures

Reactivation of Varicella-zoster virus causing shingles. (looks like strips because each nerve is responsible for a specific area?) 

• Viral Reactivation 

• Viral Reactivation 

• Two stages 

-Resumption of viral activity 

-Spread and replication 

• In HSV the virus travels down the sensory neuron to the skin or mucosal surface where it first infected 

-Infects and spreads in the sub-epithelial tissue 

-Then spreading into the epithelial tissue forming a virus-rich vesicle 

-10 – 20% of HSV re-activations may be non-lesionial with burning, tingling and itching at the site but with no signs of a cold sore 

 

VZV

In VZV changes in immune response (T-cells) can re-activate the virus which travels down the neurons to the skin and causes shingles, a painful rash 

• 10 – 20% of people who have had chickenpox develop shingles 

• Stage one (resumption of viral activity) probably occurs more than stage two (spread and replication) due to immune system control of the re-activated virus 

Latent Viral Lifestyle 

Why choose a latent viral lifestyle? 

• Let’s look at measles, which is not normally a latent infection: 

-Only infects humans 

-Does not survive long outside the body 

-There is no animal reservoir 

• Measles needs a continuous supply of fresh, susceptible humans to maintain itself, otherwise it would become extinct 

• A population size of at least 500,000 is needed to maintain measles without re-introduction from outside. 

• Latent infections are designed for survival under low population conditions 

-VZV can survive in populations as low as 1,000 individuals 

chickenpox

• Children get chickenpox 

• Virus persists in latent form in the sensory neurons 

• Later in life the virus re-activates to form shingles 

• Virus-rich lesions spread a fresh source of virus to a new, susceptible population 

• Animal reservoirs are another means of maintaining a virus in a particular area for long periods of time, especially when the virus is lethal in humans. 

-Rabies  Ebola  

(because if you rely on a human reservoir it won't work because you kill the humans they can't spread the thing) 

Viroids

Viroids - acellular pathogens of plants 

• Affects plants only, causing agricultural diseases 

• Small, circular, single-stranded RNA molecules 

• Smallest known pathogens 

• Range from 246 nucleotides in the coconut cadang-cadang viroid, to the 375-nucleotide citrus exocortis viroid 

• RNA molecule has no protein-encoding genes 

• Totally dependent on its host for replication in the host cell nucleus 

No protein and its genome is single stranded RNA (compared to viruses which have protein and the genome could be DNA or RNA) 

Prions 

The other extreme from viroids 

• Viroids are all RNA, no protein 

• Prions are all protein, no nucleic acids 

• An infectious protein, prions are known to be the cause of numerous diseases 

• Stanley Pruisner won 1997 Nobel Prize for his work on prion proteins and their disease. 

(only proteins NO genome) it is an infectious protein 

• Prions in Animals 

• Scrapie – sheep 

• Bovine spongiform encephalopathy – cows (mad cow disease) 

• Transmissible mink encephalopathy – mink 

• Chronic wasting disease – mule deer, elk 

• Prion Disease in Humans 

Creutzfeldt-Jakob disease (CJD) 

• Gerstmann-Straussler-Scheinker syndrome (GSS) 

• Fatal Familial Insomnia (FFI) 

• Kuru 

(indigenous tribe in guinea had a canabilistic ritual as a sign of respect where they ate dead  people, this caused Kuru to stay in their community because people were sometimes eating the bodt of someone who had it) 

CJD

Several different forms 

• Known since the 1920’s 

• Usually people 55 to 70 years of age affected 

• Rapid, progressive dementia 

• Vision, speech problems 

• Muscle incoordination, tremors, agitation 

• Death usually within 12 months of symptom onset 

Types of CJD 

Sporadic CJD 

-Accounts for 85% of cases 

-Arises spontaneously due to a mutation in the Prnp gene.  

-No known risk factors for developing the mutation 

• Familial CJD 

-Accounts for 10% of cases 

-Mutated version of Prnp gene is inherited. 

• Iatrogenic CJD 

-Caused by medical treatment transferring prions 

-Corneal and dura mater transplants 

-Contaminated surgical instruments 

-Growth hormone from human pituitary glands 

New Variant CJD 

New variant CJD (nvCJD or vCJD) 

• Caused by eating BSE-contaminated beef. 

• First seen in the UK in 1996 with patients unusually young    (16 – 39 years old) 

• Behavioral symptoms first: aggression, anxiety, apathy, depression, paranoid delusions or withdrawal 

• 6 months later neurological symptoms occur shaking, incontinence, immobility 

• Brain pathology more closely resembles Kuru or scrapie rather than classic CJD 

-Unusually large deposits of protein 

-Protein surrounded by halos of spongiform holes 

 

Prions 

How does a non-nucleic acid containing molecule make additional copies of itself? 

• Simplest explanation is “peer pressure” 

• Human cells have a gene (prnp) on chromosome 20 that produces a protein very similar to the prion protein 

• This protein (PrPC) is found mostly in neurons 

• Infectious prion proteins (PrPSC) can modify these normal proteins, either during or after their synthesis (S is for scrapey?) 

modifications to the normal prion protein

• Modifications to the normal prion protein include: 

-Alternative folding patterns, causing the protein to lose its normal shape and function 

-PrPC – 42% α helixes, 3% β pleated sheets 

-PrPSC – 30% α helixes, 43% β pleated sheets 

-Becomes partially resistant to proteases 

-Protein becomes insoluble