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The Minus Sense and Ambisense RNA Viruses

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1 The Minus Sense and Ambisense RNA Viruses
There are 7 families of minus strand RNA viruses All minus strand RNA viruses are enveloped with helical nucleocapsids. Families may differ in morphology of the virion, however. No polyproteins are made and the viruses do not encode proteases. Because the viral genomes are not mRNAs, all must contain enzymes within the virion to synthesize mRNA. All RNA synthesis takes place within nucleocapsids. The genome is never released free into the cytoplasm. Four families have a single piece of RNA as their genome and are grouped into the order Mononegavirales. The remaining three familes have segmented genomes. Minus strand or ambisense viruses infect vertebrates or plants. Some are arboviruses and thus infect arthropods as well.




5 Vesicular Stomatitis Virus

6 Nucleocapsids of (-)RNA Viruses

7 RNA NS L N M G Lipid Bilayer


9 Replication of Rhabdovirus RNA
Switch from mRNA synthesis to RNA replication occurs when sufficient N protein has been made to encapsidate the newly synthesized RNA. The (+)RNA is then encapsidated during synthesis and a perfect complementary copy of the genome is produced. Stop signals, poly(A) signals, reinitiation signals are all ignored. The encapsidated antigenomic RNA can be used in turn to synthesize more genomic RNA Synthesis of genomic (-)RNA also requires encapsidation of the newly synthesized RNA during synthesis. Thus, protein synthesis is required for replication of the genome but not for synthesis of mRNAs. Genomic RNA and antigenomic templates are never free but are always present in nucleocapsids, whereas mRNAs are not encapsidated.

10 Budding VSV

11 Rabies Virus The most dangereous rhabdovirus is rabies virus and its ally bat lyssavirus 50,000 humans die each year of rabies The virus is associated with wildlife--it is a zoonotic virus The virus is usually transmitted to humans by the bite of a rabid animal--there is no human-to-human transmission Bats are an important reservoir. Transmission to humans from bats may sometimes occur through aerosols. The virus first replicates around the site of the bite Transmission to the CNS may occur upon infection of axons near the site The probability of CNS infection depends upon the location of the bite Once the symptoms of rabies occur the infection is uniformly fatal Louis Pasteur developed an early vaccine against rabies A modern vaccine is widely used to prevent rabies One million people are inoculated each year following exposure Because transfer to the brain in delayed, the vaccine can be administered postexposure



14 Control of Rabies by Vaccination of Wildlife
Wildlife in areas of the U.S. and Europe have been vaccinated using baits containing vaccine. The bait contains attenuated rabies virus or contains vaccinia virus that expresses rabies G protein. The bait is often broadcast from planes. Such programs have been moderately successful in containing the spread of rabies, but are expensive and manpower-intensive.

15 Paramyxoviruses Paramyxoviruses have genomes of kb and have 8-11 (or more) genes Virions are usually spherical when grown in culture, but clinical specimens are often filamentous Six genera are currently recognized The family contains many important human pathogens Many viruses cause respiratory disease including pneumonia Mumps virus and measles virus are paramyxoviruses Two recently identified viruses cause encephalitis in humans Transmission of the viruses is by aerosols To date, only mammals and birds are known to be infected by paramyxoviruses Many are specific for a particular host Many of the human viruses infect only humans


17 SV5 Negative strain Sectioned

18 Measles virus SV5

19 Budding Filamentous Form of SV5




23 Measles virus Measles virus was once epidemic throughout the world. Very few people escaped infection by it. It is spread by aerosols and begins infection in the URT. It then becomes systemic and infects many organs. It causes a serious illness. It leads to temporary suppression of the immune system and infected persons may succumb to secondary infectionn. Infection of the CNS can lead to neurological sequella, including SSPE. Worldwide 2.5 million/year died from measles. A live vaccine, part of the MMR vaccine, has almost eradicated measles from the Americas. The virus is still epidemic in Africa and parts of Asia, however, and imported cases have resulted in small epidemics in the U.S.

24 Measles Virus History Measles virus is a human virus and humans are the only reservoir in nature. Infection results in solid, life-long immunity. Spread is by direct person-to-person contact. Therefore a minimum population size of about 500,000 is required to maintain the virus, and measles could not have existed before human populations reached this size. This may have occurred about 5000 years ago following domestication of plants and animals. When the virus was first introduced into naïve populations during European exploration years ago, the death toll was enormous. One result, aided by smallpox, was the depopulation of the Americas.



27 Trial in Senegal with High-Titer Measles Vaccine


29 Respiratory Syncytial Virus
RSV is the leading cause of pneumonia in infants worldwide. Infection begins in the URT but spreads to the LRT in ~1/3 of primary infections. Immunity following infection is incomplete and children and adults suffer recurrent infections. Disease symptoms are usually milder in second and subsequent infections, however. RSV infection of immunocompromised persons is very serious. No vaccine exists. Clinical trials with an inactivated virus vaccine gave the disastrous result that vaccinated individuals suffered more serious illness upon subsequent infection by RSV.


31 Hendra Virus and Nipah Virus
Hendra virus first appeared in Australia in 1994 Associated with an outbreak of equine respiratory disease Three humans became ill from the virus, two of whom died. Nipah virus first appeared in 1998 in Malaysia and Singapore. Causative agent of an epidemic of human encephalitis 258 cases occurred with 40% mortality rate Associated with pigs, which served as amplifying hosts These two viruses are related and flying foxes are now known to be the reservoir They represent emerging viruses that were previously unknown but suddenly appeared to cause serious human illness

32 Filoviridae

33 Filovirus Virions Marburg Virus Ebola Zaire Virus 200 nm 200 nm

34 Filovirus Outbreaks


36 Borna Disease Virus Borna disease virus is a (-)RNA virus of 9 kb.
Originally known as a pathogen of horses and sheep, it probably infects all warm blooded vertebrates. Its geographic range is probably worldwide. Infection is not cleared by the immune system and becomes chronic. Where known, it infects the CNS and produces only small amounts of virus. It is associated with abnormalities in movement and behavior. In horses, the disease may ameliorate or may progress to paralysis and death. There is preliminary evidence that the virus may be associated with neurological disease in humans, including schizophrenia and bipolar disease.

37 Borna Disease Virus 100 nm

38 Borna Disease Virus Transcription Map
Borna disease virus replicates in the nucleus and many mRNA are spliced

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