RNA RNA virusesviruses

PicornavirusesPicornavirusesPicornaviruses represent a very large Picornaviruses represent a very large

virus family with respect to the number virus family with respect to the number of members but one of the smallest in of members but one of the smallest in terms of virion size.terms of virion size.

They include two groups:They include two groups:– enterovirusesenteroviruses– rhinovirusesrhinoviruses

Enteroviruses of human Enteroviruses of human origin include the following:origin include the following:

Polioviruses, types 1-3Polioviruses, types 1-3Coxsackieviruses of group A (types Coxsackieviruses of group A (types

1-24) and B (types 1-6)1-24) and B (types 1-6)Echoviruses, types 1-34Echoviruses, types 1-34Enteroviruses, types 68-72Enteroviruses, types 68-72

Human rhinoviruses include more than Human rhinoviruses include more than 100 antigenic types.100 antigenic types.

These viruses cause upper respiratory These viruses cause upper respiratory tract infections, including common tract infections, including common cold.cold.

ReovirusesReovirusesReoviruses are medium-sized viruses.Reoviruses are medium-sized viruses.

The family Reoviridae is divided into six genera. The family Reoviridae is divided into six genera. Three of the genera are able to infect humans and Three of the genera are able to infect humans and animals:animals:– ReovirusReovirus– RotavirusRotavirus– OrbivirusOrbivirus

ArbovirusesArboviruses(arthropod-borne viruses)(arthropod-borne viruses)

The arboviruses are a group of infectious The arboviruses are a group of infectious agents that are transmitted by bloodsucking agents that are transmitted by bloodsucking arthropods from one vertabrate host to another.arthropods from one vertabrate host to another.

There are more than 450 arboviruses, of these There are more than 450 arboviruses, of these about 100 are known pathogens for humans.about 100 are known pathogens for humans.

CoronavirusesCoronavirusesCoronaviruses are large, enveloped RNA Coronaviruses are large, enveloped RNA

viruses.viruses.

The human coronaviruses cause common cold The human coronaviruses cause common cold and have been implicated in gastroenteritis in and have been implicated in gastroenteritis in infants.infants.

Coronavirus causes SARS. Coronavirus causes SARS.

RhabdovirusesRhabdovirusesRabies virus is usually transmitted to humans Rabies virus is usually transmitted to humans

from the bite of a rabid animal.from the bite of a rabid animal.

Although the number of human cases is small, Although the number of human cases is small, rabies is a major public health problem rabies is a major public health problem because it is widespread among animal because it is widespread among animal reservoirs.reservoirs.

OrthomyxovirusesOrthomyxovirusesThe orthomyxoviruses comprise Influenza A, B and The orthomyxoviruses comprise Influenza A, B and

C viruses, vhich infect human. C viruses, vhich infect human.

Formerly the orthomyxoviruses and the Formerly the orthomyxoviruses and the paramyxoviruses were grouped together in the paramyxoviruses were grouped together in the Myxovirus family. While there are some general Myxovirus family. While there are some general similarities in structure and the diseases they cause, similarities in structure and the diseases they cause, the viruses differ in a number of fundamental the viruses differ in a number of fundamental features. For this reason they were seperated into features. For this reason they were seperated into two families - the Orthomyxoviridae and two families - the Orthomyxoviridae and Paramyxoviridae.Paramyxoviridae.

Orthomyxoviruses - descriptionOrthomyxoviruses - description The virions are spherical, 80-120 nm in diameter, but may The virions are spherical, 80-120 nm in diameter, but may

be filamentous. be filamentous.

They have a helical nucleocapsid with a core of eight They have a helical nucleocapsid with a core of eight segments of single-stranded RNA. segments of single-stranded RNA.

Also present within the virion is the viral RNA-depended Also present within the virion is the viral RNA-depended RNA polymerase (this is essential for infectivity). RNA polymerase (this is essential for infectivity).

From the envelope project spikes, which attach the virion From the envelope project spikes, which attach the virion to cell receptors, as a result they are able to agglutinate to cell receptors, as a result they are able to agglutinate erythrocytes from certain species and are thus termed erythrocytes from certain species and are thus termed haemagglutinins (H). They are about 10 nm in length, with haemagglutinins (H). They are about 10 nm in length, with a molecular weight of 225000.a molecular weight of 225000.

Orthomyxoviruses - descriptionOrthomyxoviruses - descriptionBetween the haemagglutinin spikes there are Between the haemagglutinin spikes there are

mushroom-shaped protrusions of neuraminidase (N).mushroom-shaped protrusions of neuraminidase (N).

The enzyme catalyses the cleavage of NANA. This The enzyme catalyses the cleavage of NANA. This action allows the virus to permeate mucin and escape action allows the virus to permeate mucin and escape from these so-called "non-specific" inhibitors.from these so-called "non-specific" inhibitors.

Neuraminidase activity is also thought to be important Neuraminidase activity is also thought to be important in the final stages of release of new virus particules in the final stages of release of new virus particules from infected cells.from infected cells.

One of the most prominent features of the influenza One of the most prominent features of the influenza viruses is their ability to change antigenically either viruses is their ability to change antigenically either gradually over years (antigenic drift) or suddenly gradually over years (antigenic drift) or suddenly (antigenic shift). Only influenza A virus has the (antigenic shift). Only influenza A virus has the potential to shift whereas all three types may drift potential to shift whereas all three types may drift antigenically, although only very minor changes antigenically, although only very minor changes have been demonstrated in influenza C.have been demonstrated in influenza C.

The major pandemics are associated with antigenic The major pandemics are associated with antigenic shifts – when the viral H or N, or both, are changed.shifts – when the viral H or N, or both, are changed.

Orthomyxoviruses - nomenclatureOrthomyxoviruses - nomenclatureThe system of nomenclature includes the host of The system of nomenclature includes the host of

origin, geographical origin, strain number and year origin, geographical origin, strain number and year of isolation. Then follows in parentheses the of isolation. Then follows in parentheses the antigenic description of the haemagglutinin and the antigenic description of the haemagglutinin and the neuraminidase, e.g. A/swine/Iowa/3/70/(H1N1). If neuraminidase, e.g. A/swine/Iowa/3/70/(H1N1). If isolated from human host, the origin is not given, isolated from human host, the origin is not given, e.g. A/Scotland/42/89 (H3N3).e.g. A/Scotland/42/89 (H3N3).

There are 16 different H antigens and 9 N antigens. There are 16 different H antigens and 9 N antigens. Only H1-3(5) and N1-2 have been found in viruses Only H1-3(5) and N1-2 have been found in viruses from human.from human.

CultivationCultivationFor primary isolation the most suitable For primary isolation the most suitable

are tissue cultures (e.g. primary monkey are tissue cultures (e.g. primary monkey kidney or human embryo kidney cells).kidney or human embryo kidney cells).

TreatmentTreatmentOral amantadine hydrochloride was introduced in Oral amantadine hydrochloride was introduced in

the early 1980s, followed later by a derivate, the early 1980s, followed later by a derivate, rimantadine. rimantadine.

Oseltamivir (Tamiflu) and zanamivir (Relenza) can Oseltamivir (Tamiflu) and zanamivir (Relenza) can be other drug for therapy.be other drug for therapy.

Unfortunately, these compounds only have activity Unfortunately, these compounds only have activity against influenza A but not B or C.against influenza A but not B or C.

ParamyxovirusesParamyxovirusesThe paramyxoviruses include the most important The paramyxoviruses include the most important

agents of respiratory infections in infants and young agents of respiratory infections in infants and young children (RSV and the parainfluenza viruses) as well children (RSV and the parainfluenza viruses) as well as the causative agents of two of the most common as the causative agents of two of the most common contagious diseases of children (mumps and measles).contagious diseases of children (mumps and measles).

The Paramyxoviridae family can be divided into three The Paramyxoviridae family can be divided into three genera:genera:– ParamyxovirusParamyxovirus– MorbillivirusMorbillivirus– PneumovirusPneumovirus

RetrovirusesRetrovirusesThe Retrovirus family contains many viruses from The Retrovirus family contains many viruses from

widely different host species. widely different host species.

They have been studied in the laboratory for many They have been studied in the laboratory for many years, mainly because some of them are associated years, mainly because some of them are associated with tumor production in their natural hosts. Indeed, with tumor production in their natural hosts. Indeed, a wide variety of tumours are caused by the a wide variety of tumours are caused by the Oncovirus genus, including leukaemia and Oncovirus genus, including leukaemia and lymphomas, sarcomas, breast and brain tumours, lymphomas, sarcomas, breast and brain tumours, auto-immune disease and blood disorders.auto-immune disease and blood disorders.

Retroviruses - descriptionRetroviruses - description

All retroviruses have an outer envelope consisting All retroviruses have an outer envelope consisting of lipid and viral proteins. of lipid and viral proteins.

The envelope encloses the core, made of other viral The envelope encloses the core, made of other viral proteins, within which lie two molecules of viral proteins, within which lie two molecules of viral RNA and the enzyme reverse transcriptase, an RNA and the enzyme reverse transcriptase, an RNA-dependent DNA polymerase. RNA-dependent DNA polymerase.

The virions have a diameter of about 100 nm.The virions have a diameter of about 100 nm.

The retroviruses are divided into:The retroviruses are divided into:

OncovirusOncovirus– The oncoviruses include the viruses that cause The oncoviruses include the viruses that cause

tumours and a number of endogenous non-tumours and a number of endogenous non-tumour producing viruses. tumour producing viruses.

– The human viruses are HTLV-I and HTLV-II.The human viruses are HTLV-I and HTLV-II.

– A simian virus (STLV-I) is widely distributed in A simian virus (STLV-I) is widely distributed in old world monkeys.old world monkeys.

SpumavirusSpumavirus

– The spumaviruses have been detected in The spumaviruses have been detected in

various species, including cats and various species, including cats and

primates, but are not associated with primates, but are not associated with

disease.disease.

LentivirusLentivirus– The lentiviruses are so named due to their The lentiviruses are so named due to their

association with slowly progressive disease in association with slowly progressive disease in animals. animals.

– The genus includes many viruses (virus causing The genus includes many viruses (virus causing arthritis and encephalitis in goats, bovine and arthritis and encephalitis in goats, bovine and simian viruses and other). simian viruses and other).

– HIV-I and HIV-II are included. HIV-I and HIV-II are included.

– In contrast to HTVL-I, a great deal is known In contrast to HTVL-I, a great deal is known about the association of HIV infection with about the association of HIV infection with disease.disease.

Classification of HIV Classification of HIV infection and AIDSinfection and AIDS

Group I Seroconversion illness

Group II Asymptomatic

Group III Persistant generalized lymphadenopathy (PGL)

Group IV A – constitutional diseaseB – neurological diseaseC – secondary infectious diseaseD – secondary cancersE – other conditions

ReplicationReplicationRetroviruses differ from other RNA viruses in that Retroviruses differ from other RNA viruses in that

they replicate and produce viral RNA from a DNA they replicate and produce viral RNA from a DNA copy of the virion RNA.copy of the virion RNA.

Attachment of HIV to host cells is by the integration Attachment of HIV to host cells is by the integration of the external envelope glycoprotein gp120 with of the external envelope glycoprotein gp120 with part of CD4 molecule of T helper lymphocytes and part of CD4 molecule of T helper lymphocytes and other cells. other cells.

Attachment is followed by entry of the virus by Attachment is followed by entry of the virus by fusion of the two membranes, a function dependend fusion of the two membranes, a function dependend on gp41.on gp41.

ReplicationReplicationOnce the RNA is released the reverse transcriptase Once the RNA is released the reverse transcriptase

acts to form the double-stranded DNA copy, which acts to form the double-stranded DNA copy, which is circularized, enters the nucleus and is spliced into is circularized, enters the nucleus and is spliced into host cell DNA. host cell DNA.

Once inserted into the host DNA, infection with Once inserted into the host DNA, infection with HIV is permanent.HIV is permanent.

The virus may stay latent or enter a productive The virus may stay latent or enter a productive cycle.cycle.

Virus stabilityVirus stabilityHIV is inactivated by:HIV is inactivated by:

– Heat - it is destroyed in the autoclave and hot air oven.Heat - it is destroyed in the autoclave and hot air oven.– Glutaralaldehyde 2%.Glutaralaldehyde 2%.– Hypochlorite.Hypochlorite.– Several other disinfectants, including alcohols.Several other disinfectants, including alcohols.– The chemicals will kill virus within a few minutes, but is The chemicals will kill virus within a few minutes, but is

important to remember that disinfectants may not be important to remember that disinfectants may not be effective in the presence of organic material. effective in the presence of organic material.

– At room temperature virus may survive for up to 15 At room temperature virus may survive for up to 15 daysdays..

Laboratory diagnosisLaboratory diagnosisIsolation of virus in culture.Isolation of virus in culture.

The detection of viral components, e.g. p24 The detection of viral components, e.g. p24 antigen, by direct assay in the plasma or antigen, by direct assay in the plasma or detection of proviral DNA or RNA.detection of proviral DNA or RNA.

The presence of antibody to HIV antigens in The presence of antibody to HIV antigens in the serum.the serum.

TreatmentTreatmentThere is no specific therapy. There is no specific therapy.

Peptide analogues of attachment can be used Peptide analogues of attachment can be used in therapy (e.g. azidothymidine)in therapy (e.g. azidothymidine)

If T cell leukaemia or bacterial infections If T cell leukaemia or bacterial infections develop, then are managed by various drug develop, then are managed by various drug therapies.therapies.