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RNA viruses. 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. Enteroviruses of human origin include the following :.
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Picornaviruses • Picornavirusesrepresent a verylarge virus familywithrespect to thenumberofmembersbutoneofthesmallest in termsof virion size. • Theyincludetwogroups: • enteroviruses • rhinoviruses
Enterovirusesofhumanoriginincludethefollowing: • Polioviruses, types 1-3 • Coxsackievirusesofgroup A (types 1-24) and B (types 1-6) • Echoviruses, types 1-34 • Enteroviruses, types 68-72
Humanrhinovirusesinclude more than 100 antigenictypes. • These viruses cause upperrespiratorytractinfections, includingcommoncold.
Reoviruses • Reoviruses are medium-sizedviruses. • ThefamilyReoviridaeisdividedintosixgenera. Threeofthegenera are able to infecthumansandanimals: • Reovirus • Rotavirus • Orbivirus
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.
Coronaviruses • Coronaviruses are large, enveloped RNA viruses. • Thehumancoronaviruses cause commoncoldandhavebeenimplicated in gastroenteritis in infants. • Coronaviruscauses SARS.
Rhabdoviruses • Rabies virus isusuallytransmitted to humansfromthe bite of a rabidanimal. • Althoughthenumberofhumancasesissmall, rabies is a major public healthproblembecauseitiswidespreadamonganimalreservoirs.
Orthomyxoviruses • Theorthomyxovirusescomprise Influenza A, B and C viruses, vhichinfecthuman. • Formerlytheorthomyxovirusesandtheparamyxovirusesweregroupedtogether in theMyxovirusfamily. Whilethere are somegeneralsimilarities in structureandthediseasesthey cause, thevirusesdiffer in a numberoffundamentalfeatures. Forthisreasontheywereseperatedintotwofamilies - theOrthomyxoviridaeandParamyxoviridae.
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.
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.
Oneofthe most prominent featuresofthe influenza virusesistheirability to changeantigenicallyeithergraduallyoveryears (antigenic drift) orsuddenly (antigenicshift). Only influenza A virus has thepotential to shiftwhereasallthreetypesmay drift antigenically, althoughonlyveryminorchangeshavebeendemonstrated in influenza C. • The major pandemics are associatedwithantigenicshifts – whentheviral H or N, orboth, are changed.
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.
Cultivation • Forprimaryisolationthe most suitable are tissuecultures (e.g. primarymonkeykidneyorhuman embryo kidneycells).
Treatment • 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.
Paramyxoviruses • Theparamyxovirusesincludethe most importantagentsofrespiratoryinfections in infantsandyoungchildren (RSV andtheparainfluenzaviruses) as well as thecausativeagentsoftwoofthe most commoncontagiousdiseasesofchildren (mumpsandmeasles). • TheParamyxoviridaefamilycanbedividedintothreegenera: • Paramyxovirus • Morbillivirus • Pneumovirus
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.
Retroviruses - description • Allretroviruseshaveanouterenvelopeconsistingof lipid andviralproteins. • Theenvelopeenclosesthecore, madeofotherviralproteins, withinwhichlietwomoleculesofviral RNA andthe enzyme reverse transcriptase, an RNA-dependent DNA polymerase. • Thevirionshave a diameterofabout 100 nm.
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.
Spumavirus • Thespumaviruseshavebeendetected in various species, includingcatsandprimates, but are not associatedwithdisease.
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.
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.
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.
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.
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.
Treatment • Thereis no specifictherapy. • Peptide analoguesofattachmentcanbeused in therapy (e.g. azidothymidine) • If T cell leukaemiaorbacterialinfectionsdevelop, then are managed by variousdrugtherapies.