Viral properties

Dr.Sajini Souda

Human immunodeficiency virus (HIV); Aeromonas virus 31,

Influenza virus, Orf virus, Herpes simplex virus (HSV), Smallopx
virus.

Learning Objectives
Describe the nature of viruses: their small size and
diversity.
Define the following terms as used in the description and
classification of viruses: DNA virus, RNA virus, retrovirus,
capsid, enveloped, non-enveloped, symmetry.
Describe the essential features of the replication cycle for
the different groups of viruses: RNA viruses, DNA viruses
and retro viruses.
Give examples of different viruses associated with
infectious disease in humans and describe the way in which
they cause disease.
Using an example, explain how the mechanism of inhibition
by antiviral drugs can relate to specific viral properties.

Definition and Properties of a Virus

Obligate intracellular parasites.
Filterable agents.
Cannot make energy or proteins independently of a host cell.
Genomes may be RNA or DNA but not both.
Naked capsid or an envelope morphology.
Components are assembled and do not replicate by division.

Relative sizes of viruses and bacteria.

The units for measurement of virion size are nanometers (nm). The clinically important viruses range from 18 nm
(parvoviruses) to 300 nm (poxviruses) . The latter are almost visible with a light microscope and are approximately one
fourth the size of staphylococcal bacteria.
Larger virions can hold a larger genome that can encode more proteins, and they are generally more complex.

Schemes of 21 virus families infecting humans showing a number of distinctive criteria: presence of
an envelope or (double-) capsid and internal nucleic acid genome

Classification and Naming of Viruses

Viruses are classified on the basis of :
Structure: size, morphology, and nucleic acid (e.g., picornavirus
small RNA, togavirus)
Biochemical characteristics: structure and mode of replication
Disease: encephalitis and hepatitis viruses
Means of transmission: arbovirus spread by insects
Host cell (host range): animal (human, mouse, bird), plant,
bacteria
Tissue or organ (tropism): adenovirus and enterovirus

Virus Structure
Size
18 nm 300 nm diameter
Basic shape
Rod-like
Spherical (complex)
Helical
Polyhedral (Most common polyhedron is the
icosahedron which has 20 triangular faces)
Sometimes with tails or envelopes.
Genomic material
DNA or RNA
Single or double stranded
Protective Shell - Capsid
Made of many identical protein subunits
Symmetrically organized
50% of weight
Enveloped or non-enveloped

Helical Symmetry

Components of the basic virion

structure of a non enveloped icosahedral virus

(A). and an enveloped helical virus (B)

Capsid assembly of the icosahedral capsid of a picornavirus. Individual proteins

associate into subunits, which associate into protomers, capsomeres, and an
empty procapsid. Inclusion of the (+) RNA genome triggers its conversion to the

Virion Structure -Envelope

Components of the envelope
Membrane
Lipids
Proteins
Glycoproteins
Properties*
Is environmentally labiledisrupted by the
following:
Acid
Detergents
Drying
Heat
Modifies cell membrane during replication
Is released by budding and cell lysis
Consequences*
Must stay wet
Cannot survive the gastrointestinal tract
Spreads in large droplets, secretions, organ
transplants, and blood transfusions
Does not need to kill the cell to spread
May need antibody and cell-mediated
immune response for protection and control
Elicits hypersensitivity and inflammation to
cause immunopathogenesis

Virion Structure Naked Capsid

Component
Protein
Properties*
Is environmentally stable to the following:
Temperature
Acid
Proteases
Detergents
Drying
Is released from cell by lysis
Consequences*
Can dry out and retain infectivity
Can survive the adverse conditions of the
gut.
Can be spread easily (on fomites, from
hand to hand, by dust, by small droplets)
Can be resistant to detergents and poor
sewage treatment
Antibody may be sufficient for
immunoprotection

Genome
The genome of the virus consists either of
DNA
RNA
The DNA can be
Single
Double stranded
Linear
Circular
The RNA can be either
Positive sense (+) (like messenger RNA[mRNA])
Negative sense () (analogous to a photographic
negative)
Double stranded (+/)
The RNA genome may also be segmented into
pieces, with each piece encoding one or more
genes.

Properties of Virions of Human DNA Viruses

Families of DNA Viruses and Some Important

Members

RNA viruses

Properties of Virions of Human RNA Viruses

Ways in which genomic RNA of RNA viruses can be transcribed into messenger
RNA (mRNA) before translation into proteins. +ve, positive sense; -ve, negative
sense; ds, double stranded; ss, single stranded.

Translation and cleavage of viral proteins from

messenger RNA (mRNA). +ve, positive sense; ss,
single stranded.

The ways in which genomic RNA of RNA viruses is replicated. +ve, positive
sense; -ve, negative sense; mRNA, messenger RNA

Families of RNA Viruses and Some Important Members

Baltimore classification

Routes by which viruses enter the body

Mechanisms of Viral Transmission
Aerosols
Food, water
Fomites (e.g., tissues, clothes)
Direct contact with secretions
(e.g.,
saliva, semen)
Sexual contact, birth
Blood transfusion or organ
transplant
Zoonosis (animals, insects
[arboviruses])
Genetic (vertical) (e.g.
retroviruses)

Stages in the infection of a host's cell

Cell membrane receptors for virus attachment

Virus
Influenza

Rabies
HIV

Receptor molecule
Sialic acid receptor on lung epithelial cells and
upper respiratory tract
Acetylcholine receptor
Neuronal cell adhesion molecule
CD4: Primary receptor
CCR5 or CXCR4: chemokine receptors

Epstein Barr virus

C3d receptor on B cells

Human parvovirus B19

P antigen on erythoid progenitor cells

Ku80 antoantigen coreceptor

Hepatitis C virus

Epidermal growth factor receptor and ephrin

receptor A2 are host co-factors for viral entry

Human rhinoviruses

Divided into two groups based on receptor

binding:
Major group: intercellular adhesion molecule 1
(ICAM-1)
Minor group: very low density lipoprotein
receptor (VLDL-R)

Penetration and Disassembly

Mechanisms of viral entry into cells.

Nonenveloped (A) and enveloped (B) virus
internalization by receptor-mediated endocytosis.

Replication of a DNA virus-Herpes simplex virus

The virus binds to specific receptors and fuses with the

plasma membrane.

The nucleocapsid then delivers the DNA genome to the

nucleus.
Transcription and translation occur in three phases:

Immediate early

Early

Late.

Immediate early proteins promote the takeover of the

cell.

Early proteins consist of enzymes, including the DNAdependent DNA polymerase.

Late proteins are structural and other proteins, including

the viral capsid and glycoproteins.

The genome is replicated before transcription of the late

genes.

Capsid proteins migrate into the nucleus, assemble into

icosahedral capsids, and are filled with the DNA genome.

The capsids filled with genomes bud through the nuclear

and endoplasmic reticulum (ER) membranes into the
cytoplasm, acquire tegument proteins, and then acquire
their envelope as they bud through the viral glycoproteinmodified membranes of the trans- Golgi network

The virus is released by exocytosis or cell lysis.

Replication of picornaviruses: a simple (+) RNA virus.

1, Interaction of the picornaviruses with receptors on the

cell surface defines the target cell and weakens the capsid
2, The genome is injected through the virion and across th
cell membrane.
2, Alternatively, the virion is endocytosed, and then the
genome is released.
3, The genome is used as mRNA for protein synthesis. One
large polyprotein is translated from the virion genome.
4, Then the polyprotein is proteolytically cleaved into
individual proteins, including an RNA-dependent RNA
polymerase.
5, The polymerase makes a () strand template from the
genome and replicates the genome. A protein (VPg) is
covalently attached to the 5 end of the viral genome.
6, The structural proteins associate into the capsid
structure, the genome is inserted, and the virions are
released on cell lysis

Replication of Rhabdoviruses: a simple enveloped () RNA virus

1, Rhabdoviruses bind to the cell surface and are (2)

endocytosed.
The envelope fuses with the endosome vesicle membrane
to deliver the nucleocapsid to the cytoplasm.
The virion must carry a polymerase, which (3) produces fiv
individual messenger RNAs (mRNAs) and a full-length (+)
RNA template.
4, Proteins are translated from the mRNAs, including one
glycoprotein (G) which is co-translationally glycosylated in
the endoplasmic reticulum (ER), processed in the Golgi
apparatus, and delivered to the cell membrane.
5, The genome is replicated from the (+) RNA template, an
N, L, and NS proteins associate with the genome to form
the nucleocapsid.
6, The matrix protein associates with the G protein
modified membrane, which is followed by assembly of the
nucleocapsid.
7, The virus buds from the cell in a bullet-shaped virion.

Retroviral life cycle

Retroviruses have two identical copies of a plus single-stranded RNA genome and an outer envelope containing
protruding viral glycoproteins. After envelope glycoproteins on a virion interact with a specific host-cell
membrane protein or group of proteins, the retroviral envelope fuses directly with the plasma membrane
without first undergoing endocytosis (step 1). Following fusion, the nucleocapsid enters the cytoplasm of the
cell; then deoxynucleoside triphosphates from the cytosol enter the nucleocapsid, where viral reverse
transcriptase and other proteins copy the ssRNA genome of the virus into a dsDNA copy (step 2). The viral DNA
copy is transported into the nucleus (only one host-cell chromosome is depicted) and integrated into one of
many possible sites in the host-cell chromosomal DNA (step 3). The integrated viral DNA, referred to as a
provirus, is transcribed by the host-cell RNA polymerase, generating mRNAs (light red) and genomic RNA
molecules (dark red). The host-cell machinery translates the viral mRNAs into glycoproteins and nucleocapsid
proteins (step 4). The latter assemble with genomic RNA to form progeny nucleocapsids, which interact with
the membrane-bound viral glycoproteins, Eventually the host-cell membrane buds out and progeny virions are
pinched off (step 5).

Entry and spread of viruses

in human hosts.

Some major steps in viral spread and invasion of target

organs are shown. GI, gastrointestinal; HIV, human

Viral Transmission
Mode

Examples

Respiratory transmission

Paramyxoviruses, influenza viruses, picornaviruses,

rhinoviruses, varicella-zoster virus, B19 virus

Picornaviruses, rotavirus, reovirus, noroviruses,

adenovirus
Herpes simplex virus, rhinoviruses, poxviruses,
Contact (lesions, fomites)
adenovirus
Togaviruses (alpha), flaviviruses, bunyaviruses,
Zoonoses (animals, insects) orbiviruses, arenaviruses, hantaviruses, rabies virus,
influenza A virus, orf (pox)
Human immunodeficiency virus, HTLV-1, hepatitis B
Transmission via blood
virus, hepatitis C virus, hepatitis delta virus,
cytomegalovirus
Fecal-oral transmission

Sexual contact

Blood-borne viruses, herpes simplex virus, human

papillomavirus, molluscum contagiosum

Maternal-neonatal
transmission

Rubella virus, cytomegalovirus, B19 virus, echovirus,

herpes simplex virus, varicella-zoster virus, HIV

Genetic
Prions, retroviruses
HTLV-1, Human T-cell lymphotropic virus 1.

Major target tissues of viral disease.

CMV, Cytomegalovirus; EBV, EpsteinBarr virus; HHV-6, human herpesvirus
6; HIV, human immunodeficiency
virus; HSV, herpes simplex virus;
HTLV, human T-cell lymphotropic
virus; JC-PML, JC papovavirus
induced progressive multifocal
leukoencephalopathy.

Disease

Common cold (including pharyngitis)

Pharyngitis

Croup, tonsillitis, laryngitis, and bronchitis

(children younger than 2 years)
Bronchiolitis

Pneumonia

Etiologic Agent
Rhinovirus
Coronavirus
Influenza viruses
Parainfluenza viruses
Respiratory syncytial virus
Metapneumovirus
Adenovirus
Enteroviruses
Herpes simplex virus
Epstein-Barr virus
Adenovirus
Coxsackie A virus(herpangina, hand-footand-mouth disease) and other enteroviruses
Parainfluenza virus 1
Parainfluenza virus 2
Influenza virus
Adenovirus
Epstein-Barr virus
Respiratory syncytial virus(infants)
Metapneumovirus
Parainfluenza virus 3 (infants and children)
Parainfluenza viruses 1 and 2
Respiratory syncytial virus(infants)
Metapneumovirus
Parainfluenza virus(infants)
Influenza virus
Adenovirus
Varicella-zoster virus (primary infection of
adults or immunocompromised hosts)
Cytomegalovirus (infection of
immunocompromised host)
Measles

Gastrointestinal Viruses
Infants

Rotavirus A

Adenovirus 40, 41

Coxsackie A24 virus

Infants, Children, and Adults

Viruses Transmitted in Blood

Hepatitis B, C, G, D

Human immunodeficiency
virus

Human T-cell lymphotrophic

virus 1

Norwalk virus

Calicivirus

Astrovirus

Cytomegalovirus

Rotavirus A and B

Reovirus

Epstein-Barr virus

West Nile encephalitis virus

Viral Exanthems
Condition

Etiologic Agent

Rash
Rubeola

Measles virus

German measles

Rubella virus

Roseola infantum

Human herpesvirus 6

Erythema infectiosum

Human parvovirus B19

Boston exanthem

Echovirus 16

Infectious mononucleosis

Epstein-Barr virus, cytomegalovirus

Vesicles
Oral or genital herpes

Herpes simplex virus

Chickenpox/shingles

Varicella-zoster virus

Hand-foot-and-mouth disease, herpangina

Coxsackie A virus

Papillomas, etc.
Warts

Papillomavirus

Molluscum

Molluscum contagiosum

Central Nervous System Infections

Meningitis
Enteroviruses Echoviruses
Coxsackie virus
Poliovirus
Herpes simplex virus 2
Adenovirus
Mumps virus
Lymphocytic choriomeningitis virus
Arboencephalitis viruses
Paralysis
Poliovirus
Enteroviruses 70 and 71
Coxsackie A7 virus
Encephalitis
Herpes simplex virus 1
Varicella-zoster virus
Arboencephalitis viruses
Rabies virus
Coxsackie A and B viruses
Polioviruses

Postinfectious Encephalitis (Immune Mediated)

Measles virus
Mumps virus
Rubella virus
Varicella-zoster virus
Influenza viruses

Other
JC virus (progressive multifocal
leukoencephalopathy [in immunosuppressed
people])
Measles variant (subacute sclerosing
panencephalitis)
Prion (encephalopathy)
Human immunodeficiency virus (AIDS dementia)
Human T-cell lymphotropic virus 1 (tropical
spastic paraparesis)
AIDS, Acquired immunodeficiency syndrome

Sexually Transmitted Viruses

Human papillomavirus 6, 11, 42
Human papillomavirus 16, 18, 31, 45, and others (high risk for human
cervical carcinoma)
Herpes simplex virus (predominantly HSV-2)
Cytomegalovirus
Hepatitis B, C, and D viruses
Human immunodeficiency virus
Human T-cell lymphotrophic virus 1

Infections of the Organs and Tissues

Liver
Hepatitis A,* B,* C,* G, D, and E viruses

Yellow fever virus

Epstein-Barr virus
Hepatitis in the neonate or immunocompromised
person
Cytomegalovirus
Herpes simplex virus
Varicella-zoster virus

Rubella virus (congenital rubella syndrome)

Heart
Coxsackie B virus
Kidney
Cytomegalovirus

Muscle
Coxsackie B virus
(pleurodynia)
Glands
Cytomegalovirus
Mumps virus
Eye
Herpes simplex virus
Adenovirus
Measles virus
Rubella virus
Enterovirus 70
Coxsackie A24 virus

-- Arboviruses and Zoonoses

Virus

Family

Reservoir/Vector

Eastern equine encephalitis

Togaviridae

Birds/Aedes mosquito

Western equine encephalitis

Togaviridae

Birds/Culex mosquito

West Nile encephalitis

Flaviviridae

Birds/Culex mosquito

St. Louis encephalitis

Flaviviridae

Birds/Culex mosquito

California encephalitis

Bunyaviridae

Small mammals/Aedes mosquito

La Crosse encephalitis

Bunyaviridae

Small mammals/Aedes mosquito

Yellow fever

Flaviviridae

Birds/Aedes mosquito

Dengue

Flaviviridae

Monkeys/Aedes mosquito

Colorado tick fever

Reoviridae

Tick

Lymphocytic choriomeningitis

Arenaviridae

Rodents

Lassa fever

Arenaviridae

Rodents

Sin Nombre hantavirus

Bunyaviridae

Deer mice

Ebola

Filoviridae

Unknown

Rabies

Rhabdoviridae

Bats, foxes, raccoons, etc.

Influenza A

Orthomyxoviridae

Birds, swine, etc.

Chronic and Potentially Oncogenic Infections

Chronic infections occur when the immune system has difficulty resolving
the infection.
The DNA viruses (except parvovirus and poxvirus) and the retroviruses
cause latent infections with the potential for recurrence.
CMV and other herpesviruses; hepatitis B, C, G, and D viruses; and
retroviruses cause chronic infections.
HBV, HCV, EBV, HHV-8, HPV, and HTLV-1 are associated with human cancers.
HSV-2 has been associated with human cervical carcinoma, most likely as a
cofactor.
HHV-8 infection produces many cytokines to stimulate cell growth, and this
growth can progress to Kaposi sarcoma, especially in persons with AIDS.
Vaccines are now available for HBV and high-risk HPV strains.

Congenital, Neonatal, and Perinatal

Infections
The development and growth of the fetus are so ordered and rapid that a
viral infection can damage or prevent the appropriate formation of
important tissues, leading to miscarriage or congenital abnormalities.
Prenatal infection - rubella, parvovirus B19, CMV, HIV
During transit through the birth canal by contact with lesions or blood -,
HSV, HBV, CMV, HPV
Postnatal-, HIV, CMV, HBV, HSV, Coxsackie B virus, echovirus).
Rubella virus and CMV are examples of teratogenic viruses that can cause
congenital infection and severe congenital abnormalities.

Infections in Immunocompromised Patients

Patients with deficient cell-mediated immunity are generally more
susceptible to infection with enveloped viruses
Herpesviruses
Measles virus
Recurrences of infections with latent viruses (herpesviruses and
papovaviruses).
Severe T-cell deficiencies also affect the antiviral antibody response.
Viruses cause atypical and more severe presentations in
immunosuppressed people.
Infections with herpesviruses (e.g., HSV, CMV, VZV) which are normally
benign and localized, can progress locally or may disseminate and cause
visceral and neurologic infections that can be life threatening.
A measles infection might cause a giant cell (syncytial) pneumonia rather
than the characteristic rash.
People with immunoglobulin A deficiency or hypogammaglobulinemia
(antibody deficiency) have more problems with respiratory and
gastrointestinal viruses.

Laboratory Procedures for Diagnosing

Viral Infections
Cytologic examination
Electron microscopy
Virus isolation and growth
Detection of viral proteins
(antigens and enzymes)
Detection of viral genomes
Serology

Viral Cytopathologic Effects

Cell death
Cell rounding
Degeneration
Aggregation
Loss of attachments to culture dish
Characteristic histologic changes:
inclusion bodies in the nucleus or
cytoplasm, margination of chromatin
Syncytia: multinucleated giant cells
caused by virus-induced cell-to-cell
fusion
Cell surface changes
Viral antigen expression
Hemadsorption (hemagglutinin
expression)

Assays for Viral Proteins and Nucleic Acids

Proteins
Protein patterns (electrophoresis)
Enzyme activities (e.g., reverse transcriptase)
Hemagglutination and hemadsorption

Antigen detection (e.g., direct and indirect immunofluorescence, enzymelinked immunosorbent assay, Western blot)
Nucleic Acids

Restriction endonuclease cleavage patterns

Size of RNA for segmented RNA viruses (electrophoresis)
DNA genome hybridization in situ (cytochemistry)
Southern, Northern, and dot blots
PCR (DNA)
Reverse transcriptase polymerase chain reaction (RNA)
Real-time quantitative PCR

Branched-chain DNA and related tests (DNA, RNA)

Genome sequencing
DNA, Deoxyribonucleic acid; PCR, polymerase chain reaction; RNA, ribonucleic
acid.

Neutralization, hemagglutination,
and hemagglutination inhibition
assays.

In the assay shown, 10-fold

dilutions of serum were incubated
with virus.
Aliquots of the mixture were then
added to cell cultures or
erythrocytes.
In the absence of antibody, the
virus infected the monolayer
(indicated by cytopathologic effect
[CPE]) or caused hemagglutination
(i.e., formed a gel-like suspension
of erythrocytes). I
n the presence of the antibody,
infection was blocked, preventing
CPE (neutralization), or
hemagglutination was inhibited,
allowing the erythrocytes to pellet.
The titer of antibody of this serum
would be 100. pfu, Plaque-forming
units.

Western blot analysis of human immunodeficiency virus

(HIV) antigens and antibody.

(From Kuritzkes DR: Diagnostic tests for HIV infection and

resistance assays. In Cohen J, Powderly WG: Infectious

Systems for the Propagation of Viruses

People
Animals: cows (e.g., Jenner cowpox vaccine), chickens, mice, rats, suckling
mice
Embryonated eggs
Organ culture
Tissue culture
Primary
Diploid cell line
Tumor or immortalized cell line

Common Pathogenic Viruses

Specimens for Culture

Procedures and Comments

Nasal washing, throat swab, nasal swab,

sputum

RT-PCR, ELISA, multiplex assays detect

several agents; cell culture

Reovirus; rotavirus; adenovirus; Norwalk

virus, other calicivirus

Stool, rectal swab

RT-PCR, ELISA; viruses are not cultured

Maculopapular Rash
Adenovirus; enterovirus (picornavirus)
Rubella virus; measles virus
Vesicular Rash

Throat swab, rectal swab

Urine

PCR, RT-PCR
RT-PCR, ELISA

Coxsackievirus; echovirus; HSV; VZV

Vesicle fluid, scraping, or swab, enterovirus HSV and VZV: vesicle scraping (Tzanck
in stool
smear), cell culture; HSV typing by PCR, IF

Respiratory Tract
Influenza virus; paramyxoviruses;
coronavirus; rhinovirus; enterovirus
(picornavirus)
Gastrointestinal Tract

Central Nervous System (Aseptic Meningitis, Encephalitis)

Enterovirus (picornavirus)
Stool, CSF

RT-PCR

Arboviruses (e.g., togaviruses, bunyavirus) Blood, CSF; rarely cultured

RT-PCR, serology; multiplex assays detect

several agents

Rabies virus

Tissue, saliva, brain biopsy, CSF

IF of biopsy, RT-PCR

HSV; CMV; mumps virus; measles virus

Cerebrospinal fluid

PCR or RT-PCR, virus isolation, and antigen

are assayed

Urine

PCR; CMV may be shed without apparent

disease

Urinary Tract
Adenovirus; CMV
Blood
HIV; human T-cell leukemia virus; hepatitis
Blood
B, C, and D viruses, EBV, CMV, HHV-6

ELISA for antigen or antibody, PCR, and RTPCR; multiplex assays detect several agents

Targets for Antiviral Drugs

Replication Step or Target

Agent

Targeted Virus*

Attachment

Peptide analogues of attachment

protein

HIV (CCR5 co-receptor antagonist)

Neutralizing antibodies

Most viruses

Heparan and dextran sulfate

HIV, HSV

Amantadine, rimantadine

Influenza A virus

Tromantadine

HSV

Arildone, disoxaril, pleconaril

Picornaviruses

Interferon

HCVs, papillomavirus

Antisense oligonucleotides

Protein synthesis

Interferon

HCV, papillomavirus

DNA replication (polymerase)

Nucleoside analogues

Herpesviruses; HIV; hepatitis B virus,

poxviruses, etc.

Phosphonoformate, phosphonoacetic
acid

Herpesviruses

Nucleoside biosynthesis

Ribavirin

Respiratory syncytial virus, Lassa fever

virus, HCV

Nucleoside scavenging (thymidine

kinase)

Nucleoside analogues

HSV, varicella-zoster virus

Glycoprotein processing

HIV

Assembly (protease)

Hydrophobic substrate analogues

HIV, HCV

Assembly (neuraminidase)

Oseltamivir, zanamivir

Influenza A, B virus

Virion integrity

Nonoxynol-9

HIV, HSV

Penetration and uncoating

Transcription

Viruses Treatable with Antiviral Drugs

Herpes simplex virus
Varicella-zoster virus
Cytomegalovirus

Human immunodeficiency virus

Influenza A and B viruses

Respiratory syncytial virus
Hepatitis B and C viruses
Papillomavirus
Picornavirus

Thank you !!