Lecture 36. Consequence of Infection Flashcards
What are the modes of virus transmission ?
- Direct contact
- Aerosols and droplets
- Contaminated surfaces
- Vector - mosquito
- Mother to child
- Bodily fluids
How do viruses enter the body ?
- Skin
- Mucosal surfaces - respiratory, enteric, genital tract
- Eyes
- Blood
- Bites
What are the common infection patterns of acute infections ?
- Rapid onset of disease
2. Rapid production of virions, followed by clearance and elimination of infection by host
What are some examples of acute infections ?
- Poliovirus
- Influenza
- Norovirus
- Zika virus
What are the common patterns of infection of persistent infections ?
- Smouldering infections - low levels replication for many years
- Infection not cleared by host
- Virions produces continuously or intermittently
What are some examples of persistent infection ?
- HIV
2. Varicella zoster virus
What are the two types of persistent viral infections ?
- Chronic infection
2. Latent infection
What is a chronic persistent infection and give an example ?
Has a low level replication of viruses in tissues which regenerate.
Papillomavirus and cervical virus
What is a persistent latent infection and give examples?
Viral genomes are maintained but virions are not formed until episodes of reactivation
Herpes simplex in cold sores and varicella zoster virus and shingles
What are the steps in the pyramid of disease severity ?
- Asymptomatic infection
- Mild symptoms
- Sick
- Very sick
- Succumbs to virus
What is the genome of the acute measles infection ?
Negative sense single stranded RNA genome
How is acute measles transmitted ?
Respiratory droplets/aerosols
What are the symptoms of acute measles ?
Fever, cough, respiratory infection, leucopenia
What can persistent measles cause ?
Subacute sclerosing panencephalitis
What does subacute sclerosing panencephalitis cause ?
Neurological impairment, loss of control of limbs, behavioural problems, impaired eyesight, mental deterioration, seizures, paralysis, death
What is subacute sclerosing panencephalitis caused by ?
Persistent defective measles virus infection of the central nervous system
What can effect the outcome of infection ?
- Virus load
- Pathogenicity and virulence
- Virus sequence
- Host immune response/status
- Host co-morbidity (smokes, obese
- Co-infections
- Other medications
- Host genetics
- Host age, gender
What is interesting about the viral load in chicken pox ?
The first child in a family usually has it mild, the second children has a higher dose of virus and is sicker
What is pathogenicity ?
The ability of the virus to cause disease
What is virulence ?
Describes the capacity of a virus to cause disease
What are virulence determinants ?
- Enhance replication
- Modify host defense
- Facilitate spread - receptor flexibility
- Direct toxicity - diarrhoea, vomiting
What may two strands of poliovirus vary in ?
Their virulence
What does a single mutation in the genome separate in poliovirus ?
2 very different strains
What are the two strains of poliovirus ?
- Attenuated and used as a live vaccine
2. Invades the motorneurons and causes flaccid paralysis
What cancers are viruses a major contributor of ?
Liver cancer and cervical cancer
What is oncogenesis not required for ?
Replication of virus
What is oncogenesis a side effect of ?
The host response to infection
What do cancer associated viruses induce changes in ?
Cell cycle control and cell proliferation
What is viremia ?
Virus in the blood
What symptoms does minor poliovirus cause ?
Sore throat, fever, disease, malaise
Where does the major poliovirus disease enter ?
The central nervous system
Where does major poliovirus replicate ?
In motor neurons within spinal cord, brain stem or motor cortex
What are the two types of paralytic polio ?
- Spinal polio
2. Bulbospinal polio
What is spinal polio ?
Affects motor neurons responsible for movement of muscles
What is bulbospinal polio ?
Affects upper part of cervical spinal cord causing paralysis of the diaphragm - iron lung
What are some effects of acquired immune deficiency syndrome ?
- Immune deficiency - opportunistic infections and opportunistic cancers
- Wasting syndrome - Weight loss and fatigue
- Brain- AIDS dementia
How can you control viral infection ?
- Anti-viral drugs
2. Vaccines
How to reduce animal to human transmission ?
- Identify animal reservoir
- Close live animal markets
- Slaughter infected animals
- Discourage bush meat hunting and selling
How can you reduce human to human transmission ?
- Condoms , needle exchanges
- Alter funeral practices
- Travel restrictions
- Vaccination and herd immunity
What are two concepts that apply to vaccines and antiviral drugs ?
- Viruses are obligate, intracellular parasites - any intervention to host virus relationship carries inherent risks for host
- Any agent that blocks virus replication or reduces viral pathogenesis imposes selection pressures on the virus that can lead to mutations
How do antiviral drugs work ?
By blocking key steps in virus replication cycle
What must an antiviral compound do ?
Completely block viral replication
What is not acceptable for an antiviral ?
Partial inhibition
Why is partial inhibition not an acceptable antiviral ?
Viruses mutate and develop drug resistance
What are the covid treatments being approved ?
Remdesivir
How is remdesivir delivered ?
Intravenous
How does remdesivir work ?
Binds to viral RNA dependent RNA polymerase and inhibits viral replication via premature termination of RNA transcription
What are the two covid treatments being approved ?
- Molnupiravir
2. Paxloid
How does molnupiravir work ?
Acts as adapted ribonucleoside triphosphate when incorporated into RNA by viral RNA dependent RNA polymerase it results in the accumulation of errors in the viral genome, producing non-infectious virus particles
How Paxloid work ?
Protease inhibitor prevents the viral protease from cleaving viral polyproteins into functioning individual proteins
What is Paxloid delivered with and why?
Ritonavir
Slows the breakdown of the protease inhibitor
What is the aim of a vaccine ?
- Stimulate the immune system
- Prevent infection
- Prevent the spread of virus within a population
