There are a large group (more than 400) of enveloped RNA viruses which are transmitted primarily (but not exclusively) by Arthropod vectors (mosquitoes, sand-flies, fleas, ticks, lice, etc) & which were previously grouped together under the name 'Arboviruses'. More recently, this disordered assemblage has been split into 4 bona fide virus families:
||Bovine viral diarrhoea
|Hepatitis C virus
||1 serotype (variable!)
||Crimean-Congo haemorrhagic fever
||Tomato spotted wilt
Mostly, these viruses are relatively fragile (e.g. not resistant to desiccation), therefore many are reliant on vector for transmission. This dependency tends to limit them to tropical & sub-tropical regions (some exceptions - rubella, HCV).
They have complex life-cycles & replicate in both the primary hosts, secondary hosts (which may often be dead-ends) & the Arthropod vectors. Therefore, there may be several animal reservoirs for each virus - eradication would be practically impossible & the best approach is to block transmission by human vaccination/eradication of the vector (e.g. mosquitoes):
Medscape Article: Vector-Borne Disease Surveillance and Natural Disasters
All are enveloped:
- Togaviruses: Spherical, 65-70nm; Capsid: 240 monomers, icosahedral, T=4; Envelope: 80 trimer spikes, each spike = 3 x E1/E2 heterodimers, T=4 arrangement.
Image reconstruction of Semliki Forest virus.
- Flaviviruses: Spherical, 40-60nm; Capsid: Symmetry indistinct, 2 proteins: nucleocapsid ('C') and matrix ('M'); Envelope: 1 glycoprotein ('E').
- Bunyaviruses: Spherical, 80-120nm Nucleocapsid: Helical, 3 segments, 2 proteins - nucleocapsid ('N'), RNA polymerase ('L'); Envelope: 2 glycoproteins, G1 and G2, spikes less obvious.
- Arenaviruses: Pleiomorphic, 50-300nm; Nucleocapsid: As Bunyaviruses, helical; Envelope: 2 glycoprotein spikes 'GP1' 'GP2'.
- Togavirus Genomes: Single-stranded, (+)sense, non-segmented RNA, ~11.7kb, 4-8% total weight of particle. Resembles cellular mRNAs: i.e. 5' cap, 3' poly-A.
- Flavivirus Genomes: Single-stranded, (+)sense RNA, ~10.5kb. 5' cap but not polyadenylated. Genetic organization differs from Toga's - structural proteins at 5' end of genome, N.S. at 3' end.
- Bunyavirus Genomes: s/s (-)sense RNA; segmented - each virion contains 3 molecules:
- Segment / Coding capacity:
- L ~8.5kb / L, other ?
- M ~5.7kb / G1, G2, NSM
- S ~0.9kb / N, NSS
- All 3 RNA species are linear, but in the virion, appear circular because the ends are held together by base-pairing. Not present in equimolar amounts! 5' ends not capped; 3' ends not polyadenylated; genomic RNA not infectious.
- Phleboviruses: Differ from the other 4 genera (Bunyavirus, Nairovirus, Hantavirus, Tospovirus) in the following respect: Genome segment S organization is different - AMBISENSE - 5' end is (+)sense, 3' end (-)sense.
- Arenavirus Genomes: Linear, s/s RNA. Two segments - L (~5.7kb) - encodes L and Z proteins and S (~2.8kb); 5' part is (+)sense and encodes N protein; 3' part (-)sense, encodes G protein. BOTH genome segments have an ambisense organization. Replication is similar to that of Phleboviruses.
Characteristically, 2 rounds of translation:
Replication occurs in the cytoplasm and is rapid (~4h c.f. 20-30h for Flaviviruses).
Cellular receptors are not known - obviously widely distributed. Glycoprotein spikes are responsible for receptor binding - antisera neutralize attachment.
- (+)sense genomic RNA ('49S' = 11.7kb) acts directly as mRNA and is partially translated (5' end) to produce N.S. proteins.
- These proteins are responsible for replication, forming a complementary (-)strand, the template for further (+)strand synthesis.
- Two species of (+) RNA are synthesized, full length genomic RNA and sub-genomic mRNA ('26S' = 4.1kb).
- Translation of the newly synthesized sub-genomic RNA results in production of structural proteins (from 3' end of genome).
- Assembly occurs at the cell surface, and the envelope is acquired as the virus buds from the cell. Release and maturation almost simultaneous.
Initial stages are similar to Toga's (occurring in cytoplasm), but there are significant differences:
- The entire virus genome is translated as a single polyprotein which is then cleaved into the mature proteins (as Picornaviruses, c.f. Toga's).
- Complementary (-)strand RNA is synthesized by N.S. proteins, used as a template for genomic progeny RNA synthesis.
- Assembly occurs during budding, characteristically into cytoplasmic vacuoles rather than the cell surface as Toga's. Release occurs when cell lyses.
Similar to Orthomyxoviruses:
Phleboviruses: follow same basic strategy, but there are 2 rounds of transcription (one before, one after the formation of a 'reverse-sense' RNA intermediate) to cope with the ambisense coding strategy:
- i) Virus polymerase (L protein) copies genome to form:
- a) mRNA encoding N protein - 5' m7G cap is obtained by cannibalizing host cell mRNAs - like influenza.
- b) (+)sense intermediate
- ii) (+)sense intermediate is copied by L protein to form new genomic RNA.
- iii) Virus buds into Golgi vacuoles - released when cell lyses (c.f. Toga's - bud from plasmalemma, Flavi's - bud into undifferentiated cytoplasmic vacuoles).
- Host Range: Broad, grow in both mammalian and insect cell lines, characteristically producing c.p.e. in the former but not the latter (mechanism unclear). Only Alphaviruses are arthropod-borne.
- Pathogenesis: Virus is transmitted from the salivary glands of the mosquito to the bloodstream of the vertebrate host. Virus travels to the skin and reticuloendothelial system (spleen and lymph nodes), where the primary infection occurs, then viraemia follows - systemic infection. Can involve CNS (esp. encephalitis), skin/bone marrow/blood vessels (haemorrhagic fevers). Not well understood.
- Treatment: A few experimental vaccines, none commonly in use.
- Rubella virus:
- One species, quite distinct from Alphaviruses. Limited host range - mammalian cells only. First recognised as a distinct disease in 1814 (as opposed to Measles/Scarlet fever). Association with congenital abnormalities recognised by Gregg 1941 (epidemic of congenital cataracts) - the first recognition of a virus as a teratogenic agent (i.e. capable of disrupting normal foetal development). Virus isolated in 1962. Similar to other Toga's, but slightly smaller (particle 60-70nm; genome ~11kb).
- Host Range/Transmission: Can grow in a variety of mammalian cells. No known invertebrate host - man is the only reservoir, hence this virus is targeted by W.H.O. for eradication. Transmitted by aerosols - highly contagious.
- Pathogenesis: Adult infections frequently sub-clinical! Characteristic pink, continuous maculopapular rash appears in 95% of adolescent patients 14-25 days (av. 18d) after infection - patient is infectious for most of this time. After early viraemia, virus multiplies in many organs, particularly lymph nodes (lymphadenopathy), including the placenta, but symptoms in adults are rare. In children, a mild febrile illness - less severe than measles. Virus crosses placenta and multiplies in the foetus. Up to 85% of infants infected in the first trimester of pregnancy get congenital rubella syndrome (CRS) - low birth weight, deafness, CNS involvement, abortion. The earlier in pregnancy infection occurs, the worse.
- U.S. epidemic 1964: 20,000 cases of CRS - the last major epidemic in the USA (pre-vaccine).
- Foetus is persistently infected (presumably due to immature immune response) and continues to excrete virus after birth - a risk to doctors, nurses and other patients.
- Prevention/Control: A live attenuated vaccine has been used in the USA since the late 1960's and more recently in the UK (as MMR). For women infected during first trimester of pregnancy, theraputic abortion may be recommended.
- Host Range: Similar to Toga's. Can survive for long periods in hosts such as ticks by replicating in this host (without damage to the insect). In vitro, replicate in many insect and mammalian cell lines.
- Pathogenesis: Similar to Toga's, but produce a wider range of diseases - (fever; arthralgia; rash; haemorrhagic fever; encephalitis). Outcome of infection is influenced by both virus and host-specific factors (age, sex, genetic susceptibility, pre-exposure to same or related agent).
- Yellow Fever: (Latin 'flavus' = yellow). One virus, of invariant serotype, first recognised by Walter Reed, 1900 (Panama Canal). Transmitted by mosquitoes.
- Pathogenesis: Transient viraemia, primary multiplication in lymph nodes; secondary multiplication occurs in liver (jaundice), spleen, kidneys, heart and bone marrow with much tissue damage. Very debilitating, mortality ~10%. Genetic variation between different human populations results in various severity of disease, but genes involved are not known.
- 17D - live attenuated vaccine strain (Theiler 1937) - very effective. Has eradicated Yellow Fever from USA - much more difficult to tackle in central and S. America where mosquito control is less effective.
- Dengue Fever: First described 1780, virus isolated by Sabin 1944.
- At least 4 serotypes; Major health problem worldwide (Asia, Africa and America). Transmitted by mosquitoes - not affected; an infected mosquito may infect others (not via man). Primary infection produces a (relatively) mild, self-limited, febrile illness. Re-infection with a different antigenic type of the virus may result in dengue haemorrhagic fever: high fever, haemorrhagic shock, myocarditis, encephalitis; mortality ~15% - probably autoimmune mediated. No vaccine yet.
Medscape Article: "Emergence of Dengue Hemorrhagic Fever in the Americas".
Hantavirus genus: Spread from rodents (reservoir) to man by aerosolized faeces, not insect vector. These are important emergent viruses.
- More than 200 species - the largest family of viruses.
- Host range: Natural hosts include a variety of Arthropods and mammals. Can replicate extensively in insects - transovarian passage allows overwintering.
- Pathogenesis: Varied, because they are a very large group of viruses, but generally: Insect bite results in transient viraemia; replication then occurs in target organs - varies from one virus to another, as does severity (mild to severe).
- Rift Valley Fever: First isolated from sheep in E.Africa 1930. In man, produces an acute, 'flu-like illness. Transmitted by mosquitoes from animal reservoirs (e.g. sheep) to man leads to EPIZOOTICS. In the last decade, there have been massive outbreaks of R.V.F. in sub-Saharan Africa - millions of people infected, attack rates of up to 35% - more mosquitoes, more people or more domestic animals ?
Jan 16th, 1998: The U.N. Food and Agriculture Organisation (FAO) warned that an outbreak of Rift Valley Fever in Kenya and Somalia thought to have killed at least 600 people risked spreading to other parts of Africa. "A serious outbreak of Rift Valley Fever in parts of northeastern Kenya and adjacent areas of Somalia constitutes an international emergency," said a statement. According to the latest reports from the World Health Organisation (WHO), the disease has killed 300 people in Kenya and claimed another 300 lives in Somalia. Heavy flooding in parts of Kenya has brought people into closer contact than usual with animals over the past two weeks, the WHO says.
FAO said there was a high risk the disease could spread to other countries in the region.
"As well as new areas of Kenya and Somalia the countries most at risk are Sudan, Egypt, Ethiopia, Uganda and Tanzania," the statement said. The organisation warned that because mosquitos could be transported long distances on the wind there was even a risk the disease could cross the Red Sea to the Arabian peninsula. The only effective means of protecting livestock was through preventative immunisation and that vaccination once an epidemic has taken hold usually fails to prevent substantial livestock losses. There is no vaccine for humans.
To find the latest news on Rift Valley Fever,
visit "The Microbiology Newsroom"
- Sand Fly Fever (Phlebotomous Fever): Transmitted by Phlebotomous flies (sand-flies). Common in the Mediterranean - a big problem during WWII. An acute, febrile illness controlled by control of vector with insecticides.
- A relatively new family (17 types) which first came to prominence with the identification of a 'new' disease in 1969 (Lassa fever).
- Host Range: Rodent viruses - do not appear to require arthropods for spread. Do not infect insect cells.
- Pathogenesis: In natural (rodent) hosts, produce chronic (life-long) infections. Also capable of establishing a persistent infection in cell lines - a model for this type of infection.
- LCMV: A murine virus which has been studied in detail as a model for chronic virus infection. In mice, virus does not cause much cell damage. Pathogenesis is believed to result from CTL response to virus-infected cells. Rarely infects man, causing a mild disease (occasionally severe with haemorrhaging).
Lassa Fever: Natural host is small Nigerian rodent, Mastomys natalensis - transfer to man occurs via droppings (not Arthropods). Human infections (rare) are highly infectious, produce severe, systemic febrile disease with high mortality. This contrast with the rodent infection where there is apparently no pathology (virus is adapted to host).
Many Arboviruses are particularly important in that they are emerging viruses.
Emerging Infections Information Network: Thomas P.C. Monath, M.D. "The Resurgence of Yellow Fever".
© AJC 1998