RNA viruses

1. RNA viruses

2. Picornaviruses • Picornaviruses represent a very large virus family with respect to the number of members but one of the smallest in terms of virion size. • They include two groups: • enteroviruses • rhinoviruses

3. Enteroviruses of human origin include the following: • Polioviruses, types 1-3 • Coxsackieviruses of group A (types 1-24) and B (types 1-6) • Echoviruses, types 1-34 • Enteroviruses, types 68-72

4. Human rhinoviruses include more than 100 antigenic types. • These viruses cause upper respiratory tract infections, including common cold.

5. Reoviruses • Reoviruses are medium-sizedviruses. • ThefamilyReoviridaeisdividedintosixgenera. Threeofthegenera are able to infecthumansandanimals: • Reovirus • Rotavirus • Orbivirus

6. Arboviruses(arthropod-borneviruses) • Thearboviruses are a groupofinfectiousagentsthat are transmitted by bloodsuckingarthropodsfromonevertabrate host to another. • There are more than 450 arboviruses, of these about 100 are knownpathogensforhumans.

7. Coronaviruses • Coronaviruses are large, enveloped RNA viruses. • Thehumancoronaviruses cause commoncoldandhavebeenimplicated in gastroenteritis in infants. • Coronaviruscauses SARS.

8. Rhabdoviruses • Rabies virus isusuallytransmitted to humansfromthe bite of a rabidanimal. • Althoughthenumberofhumancasesissmall, rabies is a major public healthproblembecauseitiswidespreadamonganimalreservoirs.

9. Orthomyxoviruses • Theorthomyxovirusescomprise Influenza A, B and C viruses, vhichinfecthuman. • Formerlytheorthomyxovirusesandtheparamyxovirusesweregroupedtogether in theMyxovirusfamily. Whilethere are somegeneralsimilarities in structureandthediseasesthey cause, thevirusesdiffer in a numberoffundamentalfeatures. Forthisreasontheywereseperatedintotwofamilies - theOrthomyxoviridaeandParamyxoviridae.

10. Orthomyxoviruses - description • Thevirions are spherical, 80-120 nm in diameter, butmaybefilamentous. • Theyhave a helicalnucleocapsidwith a coreofeightsegmentsof single-stranded RNA. • Alsopresentwithinthe virion istheviral RNA-depended RNA polymerase (thisisessentialforinfectivity). • Fromtheenvelopeprojectspikes, whichattachthe virion to cell receptors, as a resultthey are able to agglutinateerythrocytesfromcertain species and are thustermedhaemagglutinins (H). They are about 10 nm in length, with a molecularweightof 225000.

11. Orthomyxoviruses -description • Influenza viruses bound to cells by the haemagglutinin interacting with membrane receptors containing A-acetylneuraminic acid (NANA). • Antigenic changes in the haemagglutinin have been studied by protein and nucleic acid sequencing techniques. This has shown that the antigenic changes are related to mutations of the RNA, causing amino-acid substitutions. These changes can be located in the three-dimensional structure of the molecule and are found only at a few well-definated sites close to the attachment site. These changes will of course affect antibody binding and hence the ability of the virus to infect people who have been infected, and become immune to the previous antigenic variant.

12. Orthomyxoviruses - description • Betweenthehaemagglutininspikesthere are mushroom-shapedprotrusionsofneuraminidase (N). • The enzyme catalysesthecleavageof NANA. Thisactionallowsthe virus to permeate mucin andescapefrom these so-called "non-specific" inhibitors. • Neuraminidaseactivityisalsothought to beimportant in thefinalstagesofreleaseofnew virus particulesfrominfectedcells.

13. One of the most prominent features of the influenza viruses is their ability to change antigenically either gradually over years (antigenic drift) or suddenly (antigenic shift). Only influenza A virus has the potential to shift whereas all three types may drift antigenically, although only very minor changes have been demonstrated in influenza C. • The major pandemics are associated with antigenic shifts – when the viral H or N, or both, are changed.

14. Orthomyxoviruses - nomenclature • Thesystemofnomenclatureincludesthe host oforigin, geographicalorigin, strainnumberandyearofisolation. Thenfollows in parenthesestheantigenicdescriptionofthehaemagglutininandtheneuraminidase, e.g. A/swine/Iowa/3/70/(H1N1). Ifisolatedfromhuman host, theoriginis not given, e.g. A/Scotland/42/89 (H3N3). • There are 16 different H antigensand 9 N antigens. Only H1-3(5) and N1-2 havebeenfound in virusesfromhuman.

15. Cultivation • Forprimaryisolationthe most suitable are tissuecultures (e.g. primarymonkeykidneyorhuman embryo kidneycells).

16. Treatment • Thereisstill no satisfactoryanti-influenza drug. • Oral amantadinehydrochloridewasintroduced in theearly 1980s, followedlater by a derivate, rimantadine. • Oseltamivir (Tamiflu) andzanamivir (Relenza) canbeotherdrugfortherapy. • Unfortunately, these compoundsonlyhaveactivityagainst influenza A but not B or C.

17. Paramyxoviruses • Theparamyxovirusesincludethe most importantagentsofrespiratoryinfections in infantsandyoungchildren (RSV andtheparainfluenzaviruses) as well as thecausativeagentsoftwoofthe most commoncontagiousdiseasesofchildren (mumpsandmeasles).

18. Retroviruses • The Retrovirus familycontains many virusesfromwidelydifferent host species. • Theyhavebeenstudied in thelaboratoryfor many years, mainlybecausesomeofthem are associatedwith tumor production in theirnaturalhosts. Indeed, a wide variety oftumours are caused by theOncovirus genus, includingleukaemiaandlymphomas, sarcomas, breastandbraintumours, auto-immunediseaseandblooddisorders.

19. Retroviruses - description • Allretroviruseshaveanouterenvelopeconsistingof lipid andviralproteins. • Theenvelopeenclosesthecore, madeofotherviralproteins, withinwhichlietwomoleculesofviral RNA andthe enzyme reverse transcriptase, an RNA-dependent DNA polymerase. • Thevirionshave a diameterofabout 100 nm.

20. Theretroviruses are dividedinto: • Oncovirus • Theoncovirusesincludethevirusesthat cause tumoursand a numberofendogenous non-tumourproducingviruses. • Thehumanviruses are HTLV-I and HTLV-II. • A simian virus (STLV-I) iswidelydistributed in oldworldmonkeys.

21. Spumavirus • Thespumaviruseshavebeendetected in various species, includingcatsandprimates, but are not associatedwithdisease.

22. Lentivirus • Thelentiviruses are sonameddue to theirassociationwithslowlyprogressivedisease in animals. • The genus includes many viruses (virus causing arthritis andencephalitis in goats, bovineandsimianvirusesandother). • HIV-I and HIV-II are included. • In contrast to HTVL-I, a greatdealisknownabouttheassociationof HIV infectionwithdisease.

23. Classificationof HIV infectionand AIDS

24. Replication • Retrovirusesdifferfromother RNA viruses in thattheyreplicateandproduceviral RNA from a DNA copy ofthe virion RNA. • Attachmentof HIV to host cellsis by theintegrationoftheexternalenvelopeglycoprotein gp120 with part of CD4 moleculeof T helperlymphocytesandothercells. • Attachmentisfollowed by entryofthe virus by fusionofthetwomembranes, a functiondependend on gp41.

25. Replication • Oncethe RNA isreleasedthe reverse transcriptaseacts to formthe double-stranded DNA copy, whichiscircularized, entersthenucleusandissplicedinto host cell DNA. • Onceinsertedintothe host DNA, infectionwith HIV is permanent. • The virus maystaylatentor enter a productivecycle.

26. Virus stability • HIV isinactivated by: • Heat - itisdestroyed in theautoclaveandhotairoven. • Glutaralaldehyde 2%. • Hypochlorite. • Severalotherdisinfectants, includingalcohols. • Thechemicalswillkill virus within a fewminutes, butisimportant to rememberthatdisinfectantsmay not beeffective in the presence oforganicmaterial. • Atroomtemperature virus maysurviveforup to 15 days.

27. Laboratorydiagnosis • Isolationof virus in culture. • Thedetectionofviralcomponents, e.g. p24 antigen, by directassay in the plasma ordetectionofproviral DNA or RNA. • The presence ofantibody to HIV antigens in theserum.

28. Treatment • Thereis no specifictherapy. • Peptide analoguesofattachmentcanbeused in therapy (e.g. azidothymidine) • If T cell leukaemiaorbacterialinfectionsdevelop, then are managed by variousdrugtherapies.