Positive Sense RNA Viruses

The Positive Sense RNA Viruses

• Picornaviridae (Enteroviruses, Hepatitis A virus, Rhinovirus)

• Coronaviridae (SARS, MERS)

• Togaviridae (Alphaviruses, Rubella)

• Flaviviridae (Flaviviruses-arbovirus, Hepatitis C virus)

• Caliciviridae (Norwalk-like viruses)

• Hepatitis E Virus

Picornaviridae

• Smallest RNA containing viruses

• RNA dependent RNA polymerase

• Genus

  • Enterovirus

    • Polioviruses - 3 serotypes

    • Coxsackieviruses

      • Group A - 23 serotypes

      • Group B - 6 serotypes

    • Echoviruses - 31 serotypes

    • Enteroviruses - 5 serotypes

  • Rhinovirus - more than 120 serotypes

  • Hepatovirus - Hepatitis A virus

  • Aphthovirus - Foot and mouth disease (FMD) virus

  • Cardiovirus - Encephalomyocarditis (EMC) virus

  • Unassigned - Equine rhinovirus, Drosophilia C virus

• Enteroviruses

  • Resistant to acidic pH (pH 3.0), detergents and many disinfectants including 70% alcohol

  • Formaldehyde and hypochlorite are active against enteroviruses

  • Replicate at 37 C

  • Enteroviruses cause paralytic disease, mild aseptic meningitis, exanthems, myocarditis, pericarditis, and nonspecific febrile illness

• Group Characterisitcs

  • Small (22-30 nm) in size

  • Naked capsid viruses

  • Icosahedral

  • ss (+) RNA genome with 4 major proteins

  • Replicates in the cytoplasm like (+) RNA virus

  • (+) RNA acts as mRNA and translated into a polyprotein that is cleaved by protease to various mature proteins

  • Virus assembly in the cytoplasm

  • New virus released by cell lysis

• The Virion

  • Icosahedral capsid

  • Picornaviruses typically contain four polypeptide chains (VP1, VP2, VP3, and VP4)

  • VP1, VP2, and VP3 are exposed at the virion surface wheras VP4 lies buried in close association with the RNA core

  • Proteins are arranged to form capsomeres

  • Proteins make a prominent cleft or “canyon” on its surface

  • Canyon has been shown to be the acceptor site for the receptor used by the virus to infect host cells

  • VP1 exhibits the greatest sequence variability and VP4 the least

  • VP1 is the dominant protein that plays key roles in surface topography, antigenicity, receptor attachment, and probably viral uncoating

  • Large number of picornaviruses serotypes

• The RNA Genome

  • Single stranded RNA genome

  • Naked capsid virus

  • Naked RNA is also inefective at about one millionth that of virions

  • A single break in the RNA is sufficient to destroy infectivity

• Structure of the RNA Genome

  • Consists of a single (+) RNA genome

  • Polyadenylated at 3’ terminus and carries a small protein (VPg) covalently attached to its 5’ end

  • Type 1 poliovirus was the first picornaviral RNA to be molecularly cloned into DNA and sequenced

  • A single polyprotein is encoded which is further processed to mature proteins

  • Highly conserved 5’ and 3’ nontranslated rregions (NTR) that carry signals for translation initiation and RNA synthesis

  • VPg appears to play an important role in initiation of picornaviral RNA synthesis

• The Protein Coding Region

  • A single long open reading frame encoding a long polyprotein

  • The P1 regio encoding the coat protein is ultimately cleaved into four segments

    • 1A - VP4

    • 1B - VP2

    • 1C - VP3

    • 1D - VP1

  • The P2 region encodes 2A, 2B, and 2C regions

  • 2A in poliovirus cleaves the capsid precursor prtein P1

  • 2C is involved in RNA synthesis whereas 2B is a host range determinant

  • 2C is also guanidine hydrochloride (picornavirus inhibitor) resistant marker

  • Some studies suggest that 2B and 2C are both involved in RNA synthesis and 2A is involved in shut-off of host protein synthesis

  • The P3 region encodes VPg (3B) and a proteinase (3C) and RNA polymerase (3D)

  • VPg appears to play an important role in initiation of picornaviral RNA synthesis

• Overview of Infection or Replication Cycle

  • Multiplication of Picornaviruses occur entirely in the cytoplasm

  • Step 1: Attachment of the virion to receptor units

  • Step 2: Functions of the receptor - Involving loss of VP4 protein

    • To position the virion to within striking distance

    • To trigger a conformational change in the virion

  • Step 3: Delivery of the viral RNA across the membrane

  • Step 4: Translation

  • Step 5: Synthesis of new viral RNA by copying genomic RNA to form complementary RNA

  • Step 6: Synthesis of new (+) stranded RNA

  • Step 7: Translation

  • Step 7 → Step 5 → Step 6 until a greater number of (+) stranded RNAs are made

  • Steps 8 and 9

    • Virion assembly

    • P1 is cleaved to VP0, 3, 1

    • VPg-RNA to form provirions

  • Step 10: Cleavage of VP0 to VP4 + VP2

  • Step 11: Released by infection mediated disintegration of the host cell

• Attachment, Entry, and Uncoating

  • Receptors

  • Tropism: poliovirus infects cells of nasopharynx and gut

  • Entry (receptor mediated endocytosis)

  • Uncoating

• Effects on the Host Cell

  • Contribution of the host cell: contributes energy and precursors for synthesis, receptors

  • Cytopathic effects: cellular RNA, protein, and DNA synthesis begin to decline within the first few hours of infection, full expression of CPE requires synthesis of viral protein

  • Inhibition of cellular RNA synthesis: inhibition of rRNA and mRNA declines soon after infection with many picornaviruses including poliovirus, EMC virus, human rhinovirus, and FMD

  • Poliovirus proteinase 3C modifies transcription factor complexes

• How do Picornaviruses Inhibit Synthesis of Host Proteins Without Blocking Synthesis of Viral Proteins?

  • Mechanism by which cellular protein synthesis is shut off by picornavirus by

    • Accumulation of dsRNA

    • Toxic effects of viral coat protein

    • Increas in cytoplasmsic sodium and decrease in cytoplasmic potassium

    • Inactivation of factors required for initiation of protein synthesis

    • Ability of viral RNA to outcompete host mRNA for critical components of the protein synthetic machinery

  • Poliovirus mRNA lacks the m7G cap group found at the 5’ terminus of most cellular mRNAs

  • In poliovirus infection, the cap-binding complex (CBC, p220) is inactivated which is a prerequisite for translation of most cellular RNAs by ribosomes

  • This requirement is bypassed in all picornaviruses

  • Protein 2A has been implicated in host protein shut off

• Enterovirus DIsease

  • POLIO: Spread by fecal-oral route

    • Enterovirus stable in environment and stomach acid

    • Infections peak late summer in temperate regions, young people get higher number but less serious infections

    • Virus enters oropharynx and multiplies in mucosa; shed in oral secretions and swallowed

    • Multiply in intestines → brief viremia; usually asymptomatic; recovery often occurs

    • Incubation period ranges from 4-35 days (usually 7-14 days)

    • Polio tropic for CNS

    • Motor neurons are particularly vulnerable (variable degree of destruction)

    • Three types of disease can be observed

      • Abortive poiliomyelitis

        • Nonspecific febrile illness

        • 2-3 day duration

        • No signs of CNS localization

      • Aseptic meningitis

        • No paralytic poliomyelitis

        • Stiff neck, back and pain

        • Recovery is rapid (within few days)

      • Paralytic poliomyelitis

        • Major possible outcome with a period of minor illness

        • 2 or 3 symptoms free intervening days

          • Meningeal irritation, asymmetric flaccid paralysis with no significant sensory loss

        • Variable forms; in most serious forms, all four limbs may be completely paralyzed or the brain stem may be attacked

        • Followed by paralysis of cranial nerves and muscles of respiration (bulbar polio)

        • Temporarily damaged neurons regain their function

        • Recovery begins and may continue for 6 months

        • Paralysis persisting after this time is permanant

      • Antibodies appear about day 10, same time as symptoms; neutralizing antibodies protective, block virus binding to host cell and subsequent infection

      • If immune response contains the disease, tissue replication stops but intestinal shedding can continue for weeks even with high antibody titers

      • Cell mediated immunity occurs, but viral proteins are not found on the plasma membranse of infected cells

      • Diagnosis

        • Viral isolation

        • Antibody titer

      • Prevention

        • Development of tissue culture for viral growth made possible the two polio vaccines in the 1950s

        • Killed vaccines (Salk) stimulates IgG antibodies that can eliminate the virus during viremia

        • Attenuated vaccine (Sabin) stimulates IgA response, blocks enteral spread, inexpensive, can revert to virulence, fewcases in US every year mostly dur to vaccination (1 per 2.4 million doses distributed)

        • Trivalent vaccine (3 major polio serotypes)

  • Common Clinical Diseases Associated with other Enteroviruses

    • Coxsackieviruses (A and B), Echovirus and Enterovirus

      • Unapparent infections most common (most people have antibodies)

      • Aseptic meningitis most common infection, most serious in infants, self limiting (4 to 14 days), sometimes accompanied by encephalitis which can lead to permanent neurologic sequelae

      • Enteroviruses cause the majority of nonbacterial CNS infections in the U.S.

    • Coxsackie A

      • Exanthems (Rubella-like rash), also caused by enterovirus 71

      • Herpangia (vesicles in mouth)

      • Conjunctivitis

    • Coxsackie B

      • Myocarditis and pericarditis, self limiting but may result in permanent heart damage or be fatal

      • Epidemic mulagia (pleurodynia), fever and intense upper abominal or thoracic pain

      • Generalized disease of infants , often lethal (also by Enteroviruses)

      • Evidence linked with pathogenesis of insulin-dependent diabetes mellitus

    • Some group A coxsackieviruses cause gastrointestinal syndrome in severly immunocompromised patients

  • Hepatitis A

    • Epidemiology: Worldwide

      • Higher incidence in lower socioeconomic population

    • Disease

      • Fecal-oral transmission

      • Shellfish (oysters, clams), water

      • Most infections are asymptomatic

      • Acute hepatitis

      • Replicate in small intestine, viremia

      • Onset is sudden after 14-40 day incubation

      • Fever, poor appetitie, nausea, headache, malaise, vomitng, abdominal pain

      • Jaundice (may not develop in children)

      • Dark urine

      • Enlarged liver

      • Usually self-limitng (complete recovery)

      • Immunity is complete

    • Diagnosis: Clinical picture, radioimmunoassay kits are available to detect IgM antibody for HAV

    • Prevention

      • Immune serum globulin administered before or during incubation period (Househole members, travelers going to endemic areas)

      • New Hepatitis A Vaccine (Inactivated Harvix) — Inactivated Hepatitis A virus strain HM175

Flaviviridae

• Genus

  • Flavivirus (arboviruses)
    Pestivirus (mucosal disease viruses)
    Hepacivirus (Hepatitis C virus)

• Flaviviruses

  • Members: Yellow fever virus, dengue viruses, 1-4 Zika virus, West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Russian Spring Summer virus, Powassan virus

• The Virion

  • Spherical virions of about 40 to 60 nm in diameter

  • (+) sense single stranded RNA genome surrounded by multiple copies of small basic proteins, the capsid (C)

  • Enveloped virions are composed of lipid bilayer with two or more specifics of envelope (E) proteins

  • All known viral proteins are produced as a long >3000 amino acids polypeptide, which is cleaved by a combination of host and viral proteases

  • Replication cycle not fully understood

  • Tropism and early events are not fully understood

  • In the presence of subneutralizing concentraion of antibody bound to virs, Fc receptors or C3 complement receptors can mediate attachment

  • Receptor mediated endocytosis

  • Translation, transcription

• Features of Structural Proteins

  • Virion C protein is small (11 Kd), important for nucleocapsid assembly, sequence homolgy among different flaviviruses is low but hydrophobic and hydrophilic amino acids are conserved

  • prM and M proteins: Glycosylated precursor (26 Kd) cleaved to M and pr segments, found on intracellular and extracellular virions

  • The E protein: Major envelope protein, important in virion assembly, receptor binding, membrane fusion, and principal neutralizing domain

    • The E protein is glycosylated for some, but not all, flaviviruses

• The Nonstructural Proteins

  • NS1glycoprotein exists in cell associated, cell surface, or extracellular nonvirion forms

  • Functions have not been elucidated, some role in early events of replication, mutations can affect virulence

  • NS3 (68-72 Kd) is highly conserved among flaviviruses

  • Trifunctional: protease, helicase and RNA triphosphatase activities

  • Oncogenic properties in HCV (?)

  • NS5 (103-104 Kd) is the flavivius RNA dependent RNA polymerase

  • NS2A, NS2B, NS4A, and NS4B proteins’ functions are not known

• The RNA Replication, Assembly, and Release

  • Similar to (+) RNA viruses replicating through (-) RNA intermediates

  • Ultrastructural studies suggest that virion morphogenesis occurs in association with intracellular membranes

  • Morphologically matured virions are seen within the lumn of ER

  • Virions appear to accumulate within disordrly arrays of membrane-bound vesicles

  • Secretory pathway is believed to be involved in the transport of nascent virions from the ER to the cell surface where exocytosis occurs

  • Budding of virions at the plasma membrane has been observed occasionally and does not appear to be a major mechanism for virion formation

• Effects of Flavivirus Infection on Host Cell Biology

  • In vertebrate cells, dramatic cytopathic and ultrastructural changes can occur

  • Infection is commonly cytocidal

  • Arthropod cells in culture may demonstrate cytopathic effects

  • Infection of mosquito cells is often noncytopathic and persistent infection can be establishes

• Arbovirus Disease

  • Most arboviruses are transmitted by insects

  • Three basic cycles of arbovirus transmission: urban, sylvatic, and sustained

  • Pathogenesis

    • Three major manifestations of arbovirus disease in humans

      • Viral tropisms for human organs. In some cases, the CNS is primarily affected leading to aseptic meningitis or encephalitis

      • The second syndrome involves many major organ systems with particular damage to liver as in yellow fever

      • The third is manifested by hemorrhagic fever with damage to small blood vessels and including intestinal and other hemorrhages

• Immunity

  • Rise in antibody titer generally concludes with recovery of infection

  • Neutralizing antibodies, which are the most serotype specific, generally persist many years after infection

• Specific Arbovirus Diseases Caused by Flaviviruses

  • St. Louis Encephalitis

  • Yellow Fever

  • Dengue

  • Japanese B Encephalitis

  • Powassan Virus

  • West Nile Virus

• Pathogenesis of West Nile Virus

  • Flavivirus species

  • DIstributed throughout Africa, the Middle East, parts of Europe, former USSR, India, Indonesia

  • Vector: mosquito (Tick)

  • Principal Vertebrate Host: Bird

  • Incubation period is 2 to 15 days (average 1 to 6 days)

  • Infection could be asymptomatic, West Nile Fever pr sever West Nile disease

  • 20% infected people develop West Nile fever

  • Typical case is mild characterized by fever, headache, backache, generalized myalgia

  • Rash appears in half of the cases, involving the chest, back, and upper extremities

  • Generalized lumphadenopathy is a common finding

  • Pharyngitis and gastrointestinal symptoms (nausea, vomiting, abdominal pain) may occur

  • The disease runs its course 3 to 6 days, followed by recovery

  • Children generally experience milder illness than adults

  • Severe West Nile Disease (neuroinvasive disease) West Nile encephalities, meningitis, meningo-encephalitis, West Nile poliomyelitis, 1 in 150 infected persons

  • Serious illness can occur in people over age 50 and immunocompromised

  • Symptoms may last several weeks, neurologic effects may be permanent, may also result in death

  • Clinical laboratory findings inclue leukopenia, and in cases with CNS signs, CSF pleocytosis and elevated protein

  • CCR5 chemokine receptor provides resistance to West Nile Virus infection

  • delta32CCR5 homozygosity is significantly associated with fatal outcome

  • Diagnosis: Serolofy, Confirmed by PCR

  • Treatment: Supportive

  • Antiviral and vaccine research underway

  • Has been linked to severak deaths in the United States since 1999

  • Virus found in Arizona in 2003-2004

  • Several cases in the United States and Arizona

• Hepatitis C Virus

  • Parenterally transmitted (PT) non, A-non, B hepatitis (NANBH)

  • The genome consists of a (+) stranded RNA molecule containing approximately 9,500 nucleotides with a single large ORF

  • This large ORF encodes a single large polypeptide precursor that is cleaved co- and posttranslationally to yield individual structural and nonstructural viral proteins

  • Similar genetic organization to that of flavivirus and pestivirus

  • The hydrophobicity profile of the HCV polyprotein is similar to that of flavivirus and pestivirus

  • There is substantial primary sequence identity between the 5’ terminal genomic RNA region situated upstream of the large ORF and the equivalent region in the pestiviral genomes

  • Take together, HCV is a distant relative of the pestiviruses and to a lesser extent the flaviviruses

• HCV Virion

  • HCV Structural Proteins

    • Host and viral proteases are involved in cleavages

    • C is the nucleocapsid protein (RNA binding protein)

    • E1 is the envelope glycoprotein

    • E2 is the second envelope glycoprotein

  • HCV Nonstructural Proteins

    • The putative NS proteins of HCV appear to be processed from the polyprotein through combined action of two viral encoded proteases, NS2 and the N-terminus of NS3 and appears to be metalloprotease responsible for cleavage at the junction of NS2/NS3

    • Most of the remaining cleavages that occur downstream in the polyprotein are mediated by the second protease encoded within NS3 region

    • This protease is a serine protease belonging to trypsin superfamily

    • The serine protease is responsible for cleavage at the junctions; NS3/NS4a, NS4a/NS4b, NS4b/NS5a, and NS5a/NS5b

    • NS2, NS3, and NS4a proteins interact to mediate the processing on the presumed NS regions of the polypeptide

    • The NS3 protein has also been shown to exhibit NTPase activity that is probably involved in helicase activity, based on the existence of conserved motifs with other known helicases

    • NS3 is not involved in the processing of C protein

    • NS5b contains an amino acid sequence motif (GDD) known to be highly conserved amongst RNA-dependent RNA polymerases and is thus likely to encode a similar function

    • The functions of the other NS proteins are unknown

• The 5’ and 3” UTR

  • There is a leader upstream of the AUG of ~341 nt

  • The 5’ leader represents the most highly conserved region of the HCV genome, with more than 90% homology among 81 different isolates

  • The 5’ leader may be involved in initiation of translation as predicted in pestiviruses and also seen in picornaviruses

  • The 5’ UTR can fold into a stem-loop structure

  • A pyrimidine rich region complementary to 18S ribosomal RNA exists within the apical loop of the predicted HCV structure and is similar to picornaviral internal ribosome entry sites (IRES)

  • Expression of HCV genes was efficiently mediated by 5’ UTR

  • The 3’ UTR is from 27 to 66 nt followed by a poly U sequences in most of the isolates and in some polyA

  • This region may be involved in priming the transcription of the replicative intermediate (-) strand

• Replication: Same as other (+) RNA viruses

• Pathogenesis and Immunopathogenesis

  • Originally defined as the major cause of post transfusion hepatitis

  • HCV infection commonly occurs after direct percutaneous and parenteral exposure

  • Recipients of blood or blood products, intravenous drug users, renal dialysis patients, and needle-stick victims all represent high risk of infection

  • Sexual transmission has also been suggested

  • Mother-to-infant transmision

  • Viremia generally occurs within one week after transfusion of contaminated blood or after experimental infection of chimpanzees by i.v. administration

  • In situ hybridization studies have shown the presence of genomic RNA within the hepatocytes of infected chimpanzess within 2 days after virus administration and detectable within serum 1 to days later

  • The acute phase of infection can last for several months

  • Elevations in serum aminotransferase (ALT) can occur within a few weeks of infection

  • There is growing evidence that HCV can replicated within mononuclear cells besides hepatocytes

  • Most of the serious liver disease associated with HCV is a result of the high propensity of this agent to cause chronic persistent infections

  • More than 70% HCV infected patients develop chronic infection

  • ALT remains elevated in approximately 50% of chronic cases

  • After elevation during acute phase, ALT levels generally decline during persistent infection and typically fluctuate

  • Chronic HCV leads to cirrhosis of liver and HCC

  • HCV-associated cirrhosis leads to liver failure in ~20 to 25% of cirrhotic cases

  • Prospective studies have indicated a generally slow, gradual progression from chronic active hepatitis to cirrhosis and to HCC in some patients

  • HCV RNA has been detected in tumorous tissue

  • The virus does not replicate through DNA intermediate that could conceivably integrate into the host genome and cause insertional mutagenesis

  • A high rate of viral replication results in viral heterogeneity that allows the virus to evade the immune response

  • Little evidence for direct virus-induced cytopathic effects

  • Hepatocytes are likely killed by immune mediated cytotoxic T-cells

  • Innate immune response control initital viral replication but HCV NS3/4A disrupts INF production

  • HCV core interferes with TNF receptor to decrease cytotoxic T-lymphocytes (CTL) activity

  • The natural killer (NK) cells respond to HCV infection by releasing perforins, which fragment nuclei of infected cells and induce apoptosis

  • HCV infection is inhibited by the release of interferon gamma, which recruits intrahepatic inflammatory cells, stiulates helpper T1 (Th 1) response, and induces necrosis or apoptosis of HCV-infected ccells

  • Cell-mediated and humoral responses are elicited after expression of HCV proteins, mainly necrosis or apoptosis of HCV-infected cells

  • Cell-mediated and humoral responses are elicited after expression of HCV proteins, mainly the envelope glycoproteins E1 and E2

  • HCV antibodies appear several weeks after infection, and because of selective pressure from the host, mutations take place in the E2/E1 proteins, allowing the virus to evade the humoral immune response and establish persistent infection

  • More importantly, HCV antibodies have been implicated in tissue damage because of immune complex formation

    • Examples of such tissue damage are antinuclear antibodies, autoantibodies that act against ytochrom P450 and antibodies that work against the liver and kidney

  • The immune complexes are also deposited in other tissues and cause some of the other extrahepaticc problems, including vasculitis, arthritis, glomerulonephritis, and others

  • In the absence of strong humoral immune response against HCV infection, CTL or CD8 T cells are critical to the elimination of HCV infection, and any impairment in cell-mediated immunity could be a major factor for a high level or chronicity

  • The CD8 T cells eliminate HCV by apoptosis of infected hepatocytes and interferon gamma-induced inhibition of viral replication

  • The CTL response is less effective in chronically HCV-infected patients compared with that in acutely infected patients

  • The Cd4 T cells play an important role in HCV pathogenesis by secreting several proinflammatory cytokines related to hepatocyte death

  • The chronic infection probably progresses as a result of imbalance between Th-1 and Th-2 cytokines

  • Th-1 cytokines such as interleukin 2 (IL-2) and TNF-alpha are associated with aggressive hepatic disease, wheras Th-2 cytokines (IL-10) is related to the milder presentation

    • Expression of TNF-alpha causes hepatic injury and triggers “cytokine storm” to cause liver damage in chronically infected patients

  • Host genetics play an importan role in HCV pathogenesis

  • Major histocompatibility complex (MHC) class II DR5 allele has been shown to be associated with a lower incidence of cirrhosis in HCV-infected individuals

  • One study identified CTLs restricted by HLA A2 in 97% of chronic hepatitis C patients

• Mechanisms of persistance

  • HCV and Hepatocellular carcinoma

    • HCV-infected patients may develop cirrhosis of liver with increased risk of HCC (hepatocellular carcinoma). It has also been suggested that alcoholism increases the rate of HCC in HCV infected patients

    • HCC is likely caused by long-term damage followed by rapid growth rate of hepatocytes during regeneration of liver, which may be mediated by some cytokines

      • Recent studies suggest that various HCV protein-host-cell interactions may play a role in the deveopment of HCC, including disturbance in the cell cycle, upregguation of oncogenes, and loss of tumor suppressor gene functions

    • HCV core protein has been shown to perturb and modify the growth of the cell cycle

      • HCV core interacts directly or indirectly with components or pathways that lead to oncogenesis such as tumor suppressor genes (p53, p73), protein kinase, cell cycle, and cell proliferation and differentiation

    • In addition, HCV nonstructural protein, NS5A, plays a role in cell transformation, differentiation, and oncogensis

• Clinical disease

  • 70 to 75% associated with transfusions, could be sexually transmitted

  • Acute phase is mild, asymptomatic

  • Results in chronic disease in more than 75% of patients

  • Could lead to cirrhosis of liver and hepatocellular carcinoma

• Diagnosis

  • Elevated liver enzyme alanine amino transferase (ALT)
    Antibody detection by ELISA

  • Confirmation by PCR

• Treatment

  • Interferon alpha plus ribavirin and combined with HCV protease and polymerase inhibitors

• Prevention

  • We need a vaccine

  • Development of several vaccines is underway

Coronaviridae

• Genus

  • Coronavirus (human coronaviruses causing common cold, upper respiratory tract infection, probably pneumonia, SARS, and possibly gastroenteritis)

  • Torovirus (human viruses causing enteric and respiratory disease)

• Large, enveloped (+) strand RNA viruses

• Largest genome (27 to 32 kb) of all RNA viruses

• Three serologically distinct groups of coronaviruses

• Most coronaviruses naturally infect only one species or several closely related species

• Virus replication in vivo can be disseminated, causing systemic infections, or restricted to a few cell tyoes

Togaviridae

• Genus

  • Alphavirus (Arboviruses)

  • Rubivirus (Rubella virus)

  • Arteriviruses (All animal viruses)

• Alphavirus (Hyman Pathogens)

  • Members

    • Eastern Equine Encephalitis Virus

    • Western Equine encephalitis Virus

    • Venezuelan Equine Encephalitis Virus

    • Chikungunya Virus

    • O’Nyong-Nyong Virus

    • Ross River Virus

    • Mayaro Virus

    • Sindbis Virus

• Rubivirus

  • Member: Rubella Virus

  • Rubella virus is only found in humans

  • Overall replication strategy similar to alphavirus

  • Disease (Rubella, German or 3-day measles)

    • Inhalation; Multiplies in upper respiratory tract

    • Spreads regional lymph nodes followed by viremia

    • Symptoms appear 14-21 (average 16 days) days post infection

    • Mild fever with rash

    • Rash first appears on head, neck, and trunk

    • Rash may be mild or even inapparent

    • Symptoms persist 1-3 days

    • Contagious from 7 days before to 7 days after the onset of rash

    • Immunity (generally) life-long

    • Maternal infection, Placental infection, Invasion of fetus

    • Chroic fetal infection; All organs are (may be) infected

• Arterivirus

  • All animal viruses

• Other Viruses

  • Caliciviridae (Norwalk-like Viruses) - diarrhea causing viruses

  • Hepeviridae (Hepatitis E Virus) - Enteric ally transmitted hepatitis

• Two genera-alphaviruses and rubiviruses infecting humans

• 27 different members of alphaviruses appear to have similar structure but may have distinct replication strategies

• Rubella virus is the sole member of the rubivirus genus

• Alphaviruses and rubiviruses share many features which suggest that they evolved from a common ancestor

• Enveloped animal viruses

• (+) RNA genome encapsidated in an icosahedral protein shell

• Single-Species capsid protein

• Enveloped by a lipid bilayer derived from host cell plasma membrane containing viral encoded glycoproteins E1 and E2