Basic Virus Structure: Capsid Protein Nucleocapsid Naked Capsid Virus DNA or +

Basic virus structure
DNA
or
RNA
Capsid protein
Nucleocapsid
Naked capsid virus
Nucleocapsid
Lipid membrane, glycoproteins
Enveloped virus
www.freelivedoctor.com
Properties of enveloped viruses

Envelope is sensitive to

Drying Heat Detergents Acid

Must stay wet during transmission Transmission in large droplets and secretions Cannot survive in the gastrointestinal tract Do not need to kill cells in order to spread May require both a humoral and a cellular immune response
Consequences
Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA Box 6-5
Properties of naked capsid viruses

Capsid is resistant to
Drying Heat Detergents Acids Proteases Can survive in the gastrointestinal tract Retain infectivity on drying Survive well on environmental surfaces Spread easily via fomites Must kill host cells for release of mature virus particles Humoral antibody response may be sufficient to neutralize infection
Consequences
www.freelivedoctor.com Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4
Classification of Human Viruses

"Group" dsDNA Family Poxviridae Herpesviridae Adenoviridae Polyomaviridae Papillomaviridae ssDNA Anellovirus Parvoviradae Retro Hepadnaviridae Retroviridae dsRNA Reoviridae ssRNA (-) Rhabdoviridae Filoviridae Paramyxoviridae Orthomyxoviridae Bunyaviridae Arenaviridae Deltavirus ssRNA (+) Picornaviridae Calciviridae Hepevirus Astroviridae Coronaviridae Flaviviridae Togaviridae ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA (+) (+) (+) (+) (+) (+) (+) 7 to 9 7 to 8 7 6 to 7 28 to 31 10 to 12 11 to 12 Icosahedral Icosahedral Icosahedral Isometric Helical Spherical Icosahedral No No No No Yes Yes Yes ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA (-) (-) (-) (-), segmented (-, ambi), segmented (-, ambi), segmented (-) circular 11 19 10 10 11 11 2 to 15 to 15 to 13.6 to 19 Helical Helical Helical Helical Helical Circular, nucleosomal Spherical Yes Yes Yes Yes Yes Yes Yes dsRNA, segmented 19 to 32 Icosahedral No dsDNA (partial), circular ssRNA (+), diploid 3 to 4 7 to 13 Icosahedral Spherical, rod or cone shaped Yes Yes ssDNA circular ssDNA, linear, (- or +/-) 3 to 4 5 Isometric Icosahedral No No Genome dsDNA, dsDNA, dsDNA, dsDNA, dsDNA, linear linear linear circular circular Genome size (kb) 130 to 375 125 to 240 26 to 45 5 7 to 8 Capsid Ovoid Icosahedral Icosahedral Icosahedral Icosahedral Envelope Yes Yes No No No
Variations on the replication theme
Summary: structure, classification & replication

Structure
Nucleic acid in a protein shell, +/- lipid envelope Structure impacts on biological properties
Classification
Many virus families, organized by structure and biology
Replication
Generic scheme Varying strategies depending on nucleic acid
Summary: laboratory virology

4 main clinical diagnostic techniques
Culture, serology, antigen detection, nucleic acid detection
Virus culture
Cultured cell types Cytopathic effect Not all viruses can be cultured
Virus quantitation
Biological Physical
Basic serological techniques

Cycle of infection
Entry
Primary site
Spread
Shedding
Local Lymphatic Neuronal Blood (viremia)
Secondary sites
Shedding
Time course of infection; host response

infection without spread: prodrome symptoms at primary site healing
infection with spread:
prodrome
host response: innate immunity: interferon adaptive immunity: cellular, antibody
symptoms at secondary sites
inflammatory; immunopathogenesis
2
6 time (days)
10
12
Patterns of disease
Summary: Pathogenesis & Genetics

Cycle of infection Effects on cells
Abortive, lytic, persistent, latent, transforming infections
Effects on the organism Genetics

Mutation, genotype, phenotype, reversion, recombination
For each virus, know:

Structure (cheat sheet) Pathogenesis
transmission/entry/shedding replication spread immune response/counter response damage/disease mechanism
Diagnosis Treatment/prevention
drugs vaccines
Human papillomavirus
Structure
Small (8 kb) circular dsDNA genome, naked capsid
Pathogenesis
transmission by direct contact or sexual; skin, mucosa replication in nucleus of basal cells of epithelium; very host dependent; coupled to epithelial differentiation no spread primarily cellular immune response transforming infection; warts are tumors; cervical carcinoma
Diagnosis
cytology (PAP smear; koilocytosis) immunohistochemistry nucleic acid
Prevention/treatment
recombinant subunit (VLP) vaccine PAP smear surgery
Parvovirus
Structure
Small (5 kb) linear ssDNA genome, naked capsid
Pathogenesis
respiratory transmission replication in nucleus, very host dependent, needs S phase cells or helper virus viremia antibody important in immunity targets erythroid lineage cells; fifth disease (symptoms immunological); transient aplastic crisis; hydrops fetalis
Diagnosis
serology, viral nucleic acid
Treatment/prevention
none
Polyomavirus
Structure
Small (5 kb) circular dsDNA genome, naked capsid
Pathogenesis
respiratory transmission replication in nucleus; very host dependent viremia persistence in kidneys; reactivation with immune compromise inapparent infection; hemorrhagic cystitis; PML
Diagnosis
viral nucleic acid
cidofovir ?
Adenovirus
Structure
Medium sized (36 kb) dsDNA genome, naked capsid
Pathogenesis
respiratory or fecal oral transmission replication in nucleus; moderately host dependent local spread; viremia cellular and humoral immunity important; virus encodes countermeasures against MHC I expression and apoptosis direct cell damage from replication; respiratory illness, conjunctivitis, gastroenteritis, cystitis
Diagnosis
culture, viral antigen detection
live military vaccine
Influenza
Structure
Negative sense segmented ssRNA genome, helical nucleocapsid, enveloped
Pathogenesis
respiratory transmission replication in nucleus; budding no spread (usually) innate and antibody response important; antigenic shift and drift local symptoms from cell killing; systemic symptoms from immune response; exaggerated disease in young and elderly; viral and bacterial pneumonia complications
Diagnosis
culture, hemadsorbtion, viral antigen detection
amantidine and rimantidine target matrix; zanamivir and oseltamivir target NA killed and live vaccines need constant updating
Paramyxoviruses
Structure
Negative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein and F protein
Pathogenesis
Transmission in respiratory droplets and fusion of virus envelope via F protein with plasma membrane of cells in the respiratory tract Replication in cytoplasm, budding Viremia except for RSV and PIV Innate and antibody response important; many symptoms from immune response: rash in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and pneumonia in infants Sequelae in CNS for measles and mumps
Diagnosis
Serology or nucleic acid Measles: Koplik spots; mumps: swelling of parotid gland
MMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV
Rabies
Structure
Negative sense ssRNA, helical nucleocapsid, envelope
Pathogenesis
Transmitted by bite of rabid animal Replication in cytoplasm; budding Spread by axonal transport to brain; long incubation period Fever, nausea, hydrophobia, coma Almost always fatal
Diagnosis
Viral antigen or nucleic acid, Negri bodies
Inactivated viral vaccine for humans after exposure, live virus vaccine for animals
Rotavirus
Structure
Naked double shell capsid 11 segment double stranded RNA genome
Pathogenesis
Fecal oral transmission Replication in cytoplasm Fever, vomiting, diarrhea in infants and young children Incubation period less than 48 hr, highly infectious Infection of intestinal epithelium causes loss of electrolytes and prevents readsorption of water Long term immunity; asymptomatic infection in adults
Diagnosis
viral antigen detection
RotaTeq live, oral vaccine
Summary
Paramyxoviruses
Structure Negative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein and F protein Pathogenesis Transmission in respiratory droplets and fusion of virus envelope via F protein with plasma membrane of cells in the respiratory tract Replication in cytoplasm, budding Viremia except for RSV and PIV innate and antibody response important; many symptoms from immune response: rash in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and pneumonia in infants Sequelae in CNS for measles and mumps Diagnosis serology or nucleic acid Measles Koplik spots; mumps swelling of parotid gland Treatment/prevention MMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV
Rabies
Structure Negative sense ssRNA, helical nucleocapsid, envelope Pathogenesis Transmitted by bite of rabid animal replication in cytoplasm; budding Spread by axonal transport to brain; long incubation period Fever, nausea, hydrophobia, coma Almost always fatal Diagnosis Viral antigen or nucleic acid, Negri bodies
Treatment/prevention Inactivated viral vaccine for humans after exposure, live virus vaccine for animals
Time course of Rabies infections
Rotavirus
Structure Double stranded, 11 segment RNA genome, two protein coats Pathogenesis Fecal oral transmission replication in cytoplasm Epidemic diarrhea in infants and young children- fever, vomiting, diarrhea Incubation period less than 48 hr, highly infectious Infection of intestinal epithelium causes loss of electrolytes and prevents re-adsorption of water Diagnosis culture, viral antigen detection Treatment/prevention RotaTeq live, oral vaccine
Enteroviruses
Structure Positive sense ssRNA genome, protein coat
Pathogenesis Fecal oral transmission replication in cytoplasm Viremia to diverse target tissues. Viruses very cytopathic, killing cells they infect Infections often asymptomatic; polio causes paralytic poliomyelitis; rhinoviruses restricted to upper respiratory tract, common cold; caliciviruses diarrhea
Diagnosis Serology and nucleic acid Treatment/prevention Only polio vaccines, Salk and Sabin
Arboviruses
Structure Positive sense ssRNA genome, icosahedral nucleocapsid, enveloped Pathogenesis Transmitted by bite of insect from host species; sylvan and urban cycles replication in cytoplasm; budding Viremia to target tissue Influenza-like initial symptoms; different viruses cause encephalitis, hemorrhagic fever, hepatitis, rash, arthritis Diagnosis Serology and nucleic acid Treatment/prevention No human vaccines, except yellow fever virus live attenuated vaccine, control of insect population
Arboviruses: Vectors, Hosts, and Diseases
Rubella virus
Structure Positive sense ssRNA genome, helical nucleocapsid, enveloped Pathogenesis respiratory transmission replication in cytoplasm; budding Viremia Mild rash in adults; congenital rubella syndrome (CRS) after infection in first trimester when virus passes the placenta and infects fetus CRS- deafness, blindness, mental retardation Diagnosis Nucleic acid, viral antigen detection Treatment/prevention MMR live attenuated virus vaccine
RNA Hepatitis Viruses

Structure Various different families for HAV, HCV, HEV, HGV all positive sense ssRNA Pathogenesis HAV and HEV fecal oral then viremia; others sexual and blood borne, viremia Liver is target organ; most infections are subclinical, acute infections differ in onset and severity. HAV and HEV cause hepatitis with no carrier state; others cause hepatitis with chronic infection and possible carcinoma Liver damage due to cell mediated immune response Diagnosis viral antigen detection, nucleic acid Treatment/prevention HAV killed virus vaccine; HCV alpha-interferon effective for some serotypes
HGV
///////////hepe
Flavi
Hepatitis B Virus
Structure
Small (3.2 kb) circular partially dsDNA genome, envel. capsid
Pathogenesis
Sexual, parenteral, and perinatal transmission Replication via an RNA intermediate (reverse transcriptase) Tropism for liver Acute vs. chronic infections occur: highly age dependent Chronic infections are a major cause of PHC
Diagnosis
Multiple serological components (viral proteins and anti-bodies)
Subunit vaccine (based on HBsAg)
Hepatitis B virus
Immunological events of acute vs. chronic HBV infection

A) Acute B) Chronic
From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 66, published by Mosby Philadelphia,,
Clinical interpretation of the Hepatitis B antigen panel
Hepatitis D Virus
Structure
Very Small (1.7 kb) circular ssRNA genome, envel. capsid
Pathogenesis
Sexual, parenteral, and perinatal transmission Replication by RNA-directed RNA Pol (Host RNA Pol II) Requires concurrent HBV infection (needs it for HBsAg) HDV greatly exacerbates liver damage caused by HDV Chronic infections are a major cause of PHC
Diagnosis
Serologically for HDV delta antigen
Subunit vaccine for HBV prevents productive infection
HIV
Structure
9.0 kb diploid ssRNA genome, envel. capsid
Pathogenesis
Sexual, parenteral, and perinatal transmission Replication by cDNA intermediate (reverse transcriptase) Replication cycle requires the DNA intermediate to integrate HIV establishes a persistent infection that ultimately reduces CD4 helper T cell population During course of infection, tropism shift from M-tropic to T-tropic
Diagnosis
Serologically for antibodies against HIV antigens (gp120)
Antivirals (HAART)
HIV-1 Replication Cycle

Reverse Transcription Attachment CD4 Uncoating Integration
Integrase
Reverse Transcriptase
Assembly
Budding
CCR5
Maturation
Protease
CXCR4
Beth D. Jamieson, Ph.D.
Natural Course of HIV-1 Infection
Herpesviruses
Herpes simplex I & II (cold sores, genital herpes) Varicella zoster (chicken pox, shingles) Cytomegalovirus (microcephaly, infectious mono)
Epstein-Barr virus (mononucleosis, Burkitts lymphoma)

Human herpesvirus 6 & 7 (Roseola) Human herpesvirus 8 (Kaposis sarcoma)
Human Herpesviruses
Virus Subfamily
a
Disease
Orofacial lesions
Site of Latency
Sensory Nerve Ganglia
Herpes Simplex Virus I
Herpes Simplex Virus II

Varicella Zoster Virus
a
a
Genital lesions
Chicken Pox Recurs as Shingles Microcephaly/Mono Roseola Infantum Roseola Infantum

Cytomegalovirus Human Herpesvirus 6 Human Herpesvirus 7
b b b g g
Lymphocytes CD4 T cells CD4T cells
Epstein-Barr Virus Human Herpesvirus 8
Infectious Mono Kaposis Sarcoma
B lymphocytes, salivary Kaposis Sarcoma Tissue
A study of HSV-2 recurrence in women

100 90 80 70 60 50 40 30 20 10 0
PCR HSV lesions
13
17
21
25
29
33
37
Herpesvirus Thymidine Kinase DNA
cellular enzymes
XTP's DNA replication
Vaccines live or killed?
FDA approved antiviral drugs
Non-equilibrium human virus

1. Virus has a stable relationship with an animal host. 2. Virus can be strikingly lethal since it hasnt evolved to coexist with humans. 3. Virus will be in genetic flux until it reaches equilibrium or human infection chain is broken.
4. HIV, Ebola virus, Hantavirus and Influenza virus are examples


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Basic Virus Structure: Capsid Protein Nucleocapsid Naked Capsid Virus DNA or +

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Copyright:

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Basic virus structure

Naked capsid virus

Lipid membrane, glycoproteins

Properties of enveloped viruses

Drying Heat Detergents Acid

Properties of naked capsid viruses

Classification of Human Viruses

Variations on the replication theme

Summary: structure, classification & replication

Summary: laboratory virology

Basic serological techniques

Local Lymphatic Neuronal Blood (viremia)

Time course of infection; host response

infection with spread:

symptoms at secondary sites

Summary: Pathogenesis & Genetics

Effects on the organism Genetics

For each virus, know:

Time course of Rabies infections

Arboviruses: Vectors, Hosts, and Diseases

RNA Hepatitis Viruses

Immunological events of acute vs. chronic HBV infection

Clinical interpretation of the Hepatitis B antigen panel

HIV-1 Replication Cycle

Natural Course of HIV-1 Infection

Epstein-Barr virus (mononucleosis, Burkitts lymphoma)

Herpes Simplex Virus I

Herpes Simplex Virus II

Sensory Nerve Ganglia

Cytomegalovirus Human Herpesvirus 6 Human Herpesvirus 7

Lymphocytes CD4 T cells CD4T cells

Epstein-Barr Virus Human Herpesvirus 8

Infectious Mono Kaposis Sarcoma

B lymphocytes, salivary Kaposis Sarcoma Tissue

A study of HSV-2 recurrence in women

PCR HSV lesions

Herpesvirus Thymidine Kinase DNA

XTP's DNA replication

Vaccines live or killed?

FDA approved antiviral drugs

Non-equilibrium human virus

4. HIV, Ebola virus, Hantavirus and Influenza virus are examples

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