Upload
tanyaradzwa-ngara
View
102
Download
1
Tags:
Embed Size (px)
Citation preview
Rabies Virusby
Tanyaradzwa R Ngara
Introduction
× Rabies was called lyssa or lytta, which means frenzy or madness.
× They named human rabies hydrophobia
× Rabies is a zoonotic (transmitted from animals to human) viral infectious disease.
Rabies Virus
× A group V virus
× carry their genetic material in the form of negative-sense single stranded RNA
× of the order Mononegavirales
× Rhabdovirus, Lyssavirus genus
× The family Rhabdoviridae consists of more than 185 different viruses isolated from both plants and animals
× Susceptible to disinfectants
× Inactivated by drying
Virion properties
× Contain linear, single stranded and negative sense RNA genome.
× Virions are 45-100nm in diameter, 100-430nm long.
× virion has a cylindrical nucleocapsid surrounded by an envelope with large glycoprotein spikes.
× encode for their own RNA polymerase (RNA dependent RNA polymerase).
Genome features
× The genome encodes for 5 genes in the following order.
× 3’ –N-P-M-G-L- 5’ N-
× Nucleocapsid protein
× P- Phosphoprotein- cofactor of the viral polymerase
× M- Inner virion protein/ helps in budding of the virion.
× G- Glycoprotein that assists in making virion spikes
× L- Large protein that represents RNA dependent RNA polymerase and helps in transcription and replication
Genome features
× Linear non-segmented negative sense RNA genome
× Organization of genome- 3'-Leader-Virion core- Surface proteins-Polymerase-Trailer 5'.
× Helical nucleocapsid contains the RNA dependent RNA polymerase.
× The leader RNA is neither capped nor polyadenylated and is not functional as mRNA.
Genome features
× Replication occurs when the polymerase complex ignores the transcription stop signals at the 3’ end of each gene and a full-length positive-sense anti-genome is synthesized.
× Transcription at the gene-start site is not perfect, which leads to a gradient of mRNA abundance that decreases according to the distance from the 3’ end of the genome.
Rabies virus Structure
Viral Life Cycle
Viral Life Cycle
× After receptor binding, rabies virus enters its host cells through the endosomal transport pathway.
× the low pH value induces the membrane fusion process, thus enabling the viral genome to reach the cytosol.
× Both processes of receptor binding and membrane fusion, are catalyzed by the glycoprotein G
× The first step of replication involves mRNA transcription from genomic RNA using RDRP.
Viral life cycle cont..
× For successful replication a large amount of nucleoprotein (N) and phosphoprotein (P) should be expressed.
× Switching of transcription to positive sense antigenomeoccurs after a threshold amount of N and P, which are then further used as a template for synthesis of negative stranded genomic RNA.
Viral life cycle…
× There is a single promoter site at the 3’ end of the viral genome where the polymerase attaches to the genomic RNA template and moves along the viral RNA.
× While moving it hits with start – stop signals at both the ends of the viral genes.
× Due to this only a small fraction undergoes continuous transcription process and hence this phenomenon is also known as attenuated transcription
Viral life cycle cont…
× more mRNA is produced towards the genes that are located at the 3’ end
× *hence producing a gradient of mRNA in the order of N>P>M>G>L.
× As a result of the mRNA gradient, large amount of structural protein such as nucleocapsid protein is produced as compared to L protein
Viral life cycle cont….
× Assembly and Maturation
× Nucleus
× Cytoplasm
× At membrane
Pathogenesis
× mode of transmission of rabies in man is by bite of a rabid animal or the contamination of scratch wounds by virus infected saliva.
× Replicates at site during the incubation period× Moves to nerve root endings× Replicates again× Spreads to the CNS× Vital nerve centers infected - irritable/aggressive× Direct transmission of virus occurs from cell to cell across
synaptic junctions.× Centrifugal spread to salivary glands, skin, etc.× Secreted with saliva communicable× Fatality can occur from two days to five years from the time of
initial infection.
General Symptoms
× Fever
× Headache
× Weakness
× Discomfort
× * Usually exhibited for 2-10 days
More Severe Symptoms
× Insomnia
× Anxiety
× Confusion
× Slight or Partial Paralysis
× Hallucinations
More Severe Symptoms
× Excitation
× Agitation
× Hypersalivation
× Difficulty Swallowing
× Hydrophobia
× * Death usually occurs within days of the onset of the more severe symptoms
Rabies in Animals
Rabid Animals By Frequency
× Dogs
× Raccoons
× Skunks
× Bats
× Foxes
× Rodents & Lagomorphs
Types of Exposure
× Bites
× Non-bites exposure: contamination of open wounds, abrasions, mucous membranes or, theoretically, scratches (potentially contaminated with infectious material from a rabid animal)
× Human to Human Transmission
Epidemiology Global Distribution of lyssaviruses
Epidemiology cont…
× Most of the developing countries in Asia are the victims of rabies.
× 55 000 deaths in Africa and Asia yearly (WHO, 2011)
× One Asian dies every 15 minutes where 15% are likely to be the children under 15 years
× in Bangladesh also where nearly 100,000 people being bitten by dogs in 2009 and 3,000 died of rabies
× In India, about 15 million people are bitten by dogs every year
Epidemiology cont…
Rabies in Africa
× Rabies causes at least 24,000 deaths per year in Africa (WHO, 2013)
× The major cause of spread of rabies in this region is urbanization
× In Rwanda an estimation of 127 Human dog bites was reported (Ministry of Health)
× Most southern African countries like; Angola, Namibia, Mozambique, Zimbabwe are also considered as high risk areas.
Treatment
• After Exposure
× Post exposure treatment consists of
× Local treatment of the wound
× Adminstration of rabies immunoglobins
× Immediate vaccination
Treatment..
× Local Treatment of the wound
• Wash wounds immediately with soap & water
This is the most effective way to decrease the chance of infection
Treatment…
× Patient with confirmed cases of rabies should be
× isolated,
× sedated and transferred to appropriate medical facility
Treatment
Primary Vaccinations
Treatment cont…..
Primary Vaccinations
× Three 1.0-mL injections of HDCV or PCEC vaccine should be administered intramuscularly (deltoid area) -- one injection per day on days 0, 7, and 21 or 28
Treatment
Passive Immunization
× Horse Anti Rabies serum
× Human Rabies immunoglobin (HRIG)
× Booster doses are essential whenever anti rabies serum is given with the vaccine
Prevention
• Eliminating rabies in dogs
× eliminating rabies in dogs through vaccination
× This has reduced the number of human rabies cases in most Latin America
× However recent increases in human rabies deaths suggest that rabies is emerging as a serious public health issue
Prevention cont..
× prevention of human rabies through control of domestic dog rabies is a realistic goal
• Preventive immunization in people
× Safe, effective vaccines also exist for human use
× Pre-exposure immunization in people (Travellers to high-risk areas in rabies affected countries, animals handlers, veterinarians in rabies affected areas
Prevention cont…
• Epidemiological surveillance× Dog bites must be notifiable within national surveillance system
on weekly basis× Collected data should be processed and disseminated rapidly
between different administrative levels
• Steps to be taken after reporting a dog bite× Dog movement: stray or restricted dog?× Circumstances around the bite: is the dog provoked or not?× Dog vaccination status× The offending dog should be contained and observed for 14
days
Applications in Gene Therapy
Neuronal gene transfer
× To treat cardiovascular regions of CNS tissue
× Spinal cord regeneration
Thank You