Arboviruses

R.Varidianto Yudo T., dr.,MKesR.Varidianto Yudo T., dr.,MKes

Lab. Mikrobiologi Lab. Mikrobiologi

Fakultas Kedokteran Universitas Hang Fakultas Kedokteran Universitas Hang TuahTuah

The term “arbovirus” (arthropodborne virus) was originally used as a synonym for togavirus.

The term "arbovirus" is an acronym for arthropod-borne virus and highlights the fact that these viruses are transmitted by arthropods, primarily mosquitoes and ticks.

It is now no longer an official taxon since it refers only to the arthropod vectors, whereas the variety of virus types transmitted by this route is much greater, including for instance togavirus as well as flavivirus types.

The arboviruses are transmitted by The arboviruses are transmitted by bloodsucking arthropods from one vertebrate bloodsucking arthropods from one vertebrate host to another. host to another.

The vector acquires a lifelong infection through The vector acquires a lifelong infection through the ingestion of blood from a viremic the ingestion of blood from a viremic vertebrate. vertebrate.

The viruses multiply in the tissues of the The viruses multiply in the tissues of the arthropod without evidence of disease or arthropod without evidence of disease or damage. damage.

Some arboviruses are maintained in nature by Some arboviruses are maintained in nature by transovarian transmission in arthropods.transovarian transmission in arthropods.

Most arboviruses are classified in 2 Most arboviruses are classified in 2 Families, namely togaviruses and Families, namely togaviruses and bunyaviruses bunyaviruses

(1) Togaviruses are characterized by (1) Togaviruses are characterized by an an icosahedral nucleocapsidicosahedral nucleocapsid surrounded by an envelope and surrounded by an envelope and a a single-stranded, positive-polarity single-stranded, positive-polarity RNA genomeRNA genome. .

This family is subdivided into 4 genera on This family is subdivided into 4 genera on the basis of size and antigenic the basis of size and antigenic relationships: relationships:

alphavirusesalphaviruses (60- 70 nm) (60- 70 nm) rubiviruses (60- 70 nm)rubiviruses (60- 70 nm) flavivirusesflaviviruses (45-55 nm) (45-55 nm) It became family !! It became family !! pestiviruses (45-55 nm). pestiviruses (45-55 nm).

Only alphaviruses and flaviviruses are Only alphaviruses and flaviviruses are considered here. considered here.

The only rubivirus is rubella virus and The only rubivirus is rubella virus and pestiviruses do not cause human disease.pestiviruses do not cause human disease.

(2) Bunyaviruses have a (2) Bunyaviruses have a helical helical nucleocapsidnucleocapsid surrounded by an surrounded by an envelope and a genome consisting of envelope and a genome consisting of 3 segments of negative-polarity RNA3 segments of negative-polarity RNA that are hydrogen-bonded together.that are hydrogen-bonded together.

Classification of the major Classification of the major arbovirusesarboviruses

Family Genus Viruses of Medical Interest

Togavirus Alphavirus Chikungunya, Eastern equine encephalitis virus, Western equine encephalitis virus, Mayaro, O'Nyong-Nyong, Ross River, Semliki Forest viruses.

Flavivirus Flavivirus Dengue virus, St. Louis encephalitis virus, yellow fever virus, West Nile virus

Bunyavirus Bunyavirus California encephalitis virus

Reovirus Orbivirus Colorado tick fever virus

TRANSMISSIONTRANSMISSION The life cycle of the arboviruses is based The life cycle of the arboviruses is based

on the ability of these viruses to on the ability of these viruses to multiply multiply in both the vertebrate host and the in both the vertebrate host and the bloodsucking vectorbloodsucking vector. .

For effective transmission to occur, the For effective transmission to occur, the virus must be present in the bloodstream virus must be present in the bloodstream of the vertebrate host (viremia) in of the vertebrate host (viremia) in sufficiently high titer to be taken up in the sufficiently high titer to be taken up in the small volume of blood ingested during an small volume of blood ingested during an insect bite. insect bite.

After ingestion, the virus replicates in the After ingestion, the virus replicates in the gut of the arthropod and then spreads to gut of the arthropod and then spreads to other organs, including the salivary glands. other organs, including the salivary glands.

Only the female of the species serves as the Only the female of the species serves as the vector of the virus, because only she vector of the virus, because only she requires a blood meal in order for progeny requires a blood meal in order for progeny to be produced. to be produced.

An obligatory length of time called An obligatory length of time called the the extrinsic incubation periodextrinsic incubation period, must pass , must pass before the virus has replicated sufficiently before the virus has replicated sufficiently for the saliva of the vector to contain for the saliva of the vector to contain enough virus to transmit an infectious dose. enough virus to transmit an infectious dose.

For most viruses, the extrinsic incubation For most viruses, the extrinsic incubation period ranges from 7 to 14 days.period ranges from 7 to 14 days.

In addition to transmission through In addition to transmission through vertebrates, some arboviruses are vertebrates, some arboviruses are transmitted by vertical "transovarian" transmitted by vertical "transovarian" passage from the mother tick to her passage from the mother tick to her offspring. offspring.

Vertical transmission has important survival Vertical transmission has important survival value for the virus if a vertebrate host is value for the virus if a vertebrate host is unavailable.unavailable.

Humans are involved in the transmission Humans are involved in the transmission cycle of arboviruses in 2 different ways. cycle of arboviruses in 2 different ways.

Usually, humans are "dead-end" hosts, Usually, humans are "dead-end" hosts, because the concentration of virus in human because the concentration of virus in human blood is too low and the duration of viremia blood is too low and the duration of viremia too brief for the next bite to transmit the too brief for the next bite to transmit the virus. virus.

However, in some diseases, eg, yellow However, in some diseases, eg, yellow fever and dengue, humans have a high-fever and dengue, humans have a high-level viremia and act as reservoirs of the level viremia and act as reservoirs of the virus. virus.

Infection by arboviruses usually does not Infection by arboviruses usually does not result in disease either in the arthropod result in disease either in the arthropod vector or in the vertebrate animal that vector or in the vertebrate animal that serves as the natural host. serves as the natural host.

Disease occurs primarily when the virus Disease occurs primarily when the virus infects dead-end hosts. infects dead-end hosts.

CLINICAL FINDINGS & CLINICAL FINDINGS & EPIDEMIOLOGYEPIDEMIOLOGY

The diseases caused by arboviruses The diseases caused by arboviruses range in severity from mild to range in severity from mild to rapidly fatal.rapidly fatal.

The clinical picture usually fits one The clinical picture usually fits one of 3 categories: of 3 categories:

1.1. EncephalitisEncephalitis

2.2. Hemorrhagic fever; or Hemorrhagic fever; or

3.3. Fever with myalgias, arthralgias, and Fever with myalgias, arthralgias, and nonhemorrhagic rash nonhemorrhagic rash

The pathogenesis of these diseases The pathogenesis of these diseases involves not only the cytocidal effect involves not only the cytocidal effect of the virus but also, in some, a of the virus but also, in some, a prominent immunopathologic prominent immunopathologic component. component.

Following recovery from the disease, Following recovery from the disease, immunity is usually lifelong.immunity is usually lifelong.

DENGUE VIRUSDENGUE VIRUS Classic dengue ("breakbone fever")Classic dengue ("breakbone fever")

begins suddenly with an influenzalike begins suddenly with an influenzalike syndrome consisting of fever, malaise, syndrome consisting of fever, malaise, cough, and headache. cough, and headache.

Severe pains in muscles and joints Severe pains in muscles and joints (breakbone) occur. (breakbone) occur.

Enlarged lymph nodes, a maculopapular Enlarged lymph nodes, a maculopapular rash, and leukopenia are common. rash, and leukopenia are common.

After a week or so, the symptoms regress After a week or so, the symptoms regress but weakness may persist. but weakness may persist.

Although unpleasant, this typical form of Although unpleasant, this typical form of dengue is rarely fatal and has few sequelae.dengue is rarely fatal and has few sequelae.

In contras, In contras, dengue hemorrhagic feverdengue hemorrhagic fever is a is a much more severe disease, with a fatality much more severe disease, with a fatality rate that approaches 10%. rate that approaches 10%.

The initial picture is the same as classic The initial picture is the same as classic dengue, but then shock and hemorrhage, dengue, but then shock and hemorrhage, especially into the gastrointestinal tract and especially into the gastrointestinal tract and skin, develop. skin, develop.

Dengue hemorrhagic fever occurs particularly Dengue hemorrhagic fever occurs particularly in in southern Asiasouthern Asia, whereas the classic form , whereas the classic form is found in tropical areas worldwide.is found in tropical areas worldwide.

Hemorrhagic shock syndromeHemorrhagic shock syndrome is due to the is due to the production of large amounts of production of large amounts of cross-reacting cross-reacting antibodyantibody at the time of a second dengue infection. at the time of a second dengue infection.

The pathogenesis is as follows: The patient recovers The pathogenesis is as follows: The patient recovers from classic dengue caused by one of the 4 serotypes, from classic dengue caused by one of the 4 serotypes, and antibody against that serotype is produced. and antibody against that serotype is produced.

When the patient is infected with another serotype of When the patient is infected with another serotype of dengue virus, an anamnestic, heterotypic response dengue virus, an anamnestic, heterotypic response occurs and large amounts of cross-reacting antibody occurs and large amounts of cross-reacting antibody to the first serotype are produced. to the first serotype are produced.

Immune complexes composed of virus and antibody Immune complexes composed of virus and antibody are formed that activate complement, causing are formed that activate complement, causing increased vascular permeability and increased vascular permeability and thrombocytopenia. thrombocytopenia.

Shock and hemorrhage result. Shock and hemorrhage result.

Dengue virus is transmitted by the Dengue virus is transmitted by the AedesAedes aegyptiaegypti mosquito, which is also the vector mosquito, which is also the vector of yellow fever virus. of yellow fever virus.

Human are the reservoir for dengue virus, Human are the reservoir for dengue virus, but a jungle cycle involving monkeys as the but a jungle cycle involving monkeys as the reservoir and other reservoir and other AedesAedes species as species as vectors is suspected.vectors is suspected.

No antiviral therapy or vaccine for dengue No antiviral therapy or vaccine for dengue is available. is available.

Outbreaks are controlled by using Outbreaks are controlled by using insecticides and draining stagnant eater insecticides and draining stagnant eater that serves as the breeding place for the that serves as the breeding place for the mosquitoes.mosquitoes.

Properties of FlavivirusesProperties of Flaviviruses Flaviviruses show morphological uniformity with an

icosahedral capsid and closefitting, spiked envelope.

The size of the capsid is about 30 nm and the whole virion measures 45 nm.

The genome of the flaviviruses is a single stranded, (+) sense RNA about 10 kb in size.

It codes for three structural and seven nonstructural proteins.

Both cotranslational and posttranslational protein processing, similar to what is seen in the picornaviruses, has been described.

The morphogenesis of the virus occurs at the endoplasmic reticulum, into the lumen of which the finished viruses bud.

ReferencesReferences

Levinson W, 2004. Medical Microbiology & Levinson W, 2004. Medical Microbiology & Immunology: Examination & Board Review, Immunology: Examination & Board Review, Eighth Edition. McGraw-Hill Companies, Inc., USAEighth Edition. McGraw-Hill Companies, Inc., USA

Brooks G.F., Butel J.S., Morse S.A., 2001. Jawetz, Brooks G.F., Butel J.S., Morse S.A., 2001. Jawetz, Melnick and Adelberg’s Medical Microbiology Melnick and Adelberg’s Medical Microbiology (22nd ed.). USA. Appleton & Lange (22nd ed.). USA. Appleton & Lange