general characteristics of RNA viruses.pptx

General Virology and
Overview of Viral Infections

GENERAL PROPERTIES OF
VIRUSES
2

Essentials of Medical Microbiology by Apurba S Sastry © Jaypee Brothers Medical Publishers
GENERAL PROPERTIES OF VIRUSES
3
▰ Smallest unicellular organisms that are obligate intracellular.
▰ Viruses are the most primitive microorganisms infecting man.

Viruses differ from bacteria as:
4
▰ Obligate intracellular
▰ Possess either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), but
never both
▰ Smaller than bacteria, can be passed through the bacterial filters
▰ Cannot be grown on artificial cell free media (grow in animals, embryonated
eggs or tissue culture)

Viruses differ from bacteria as (Cont..):
5
▰ Multiply by a complex method (not by binary fission).
▰ Do not have a proper cellular organisation.
▰ Do not have cell wall or cell membrane or cellular organelles including
ribosomes
▰ Lack the enzymes necessary for protein and nucleic acid synthesis.
▰ Not susceptible to antibacterial antibiotics

MORPHOLOGY OF VIRUS
7
▰ The entire virus particle called as virion, comprises of a nucleic acid (DNA or
RNA) surrounded by a protein coat called as capsid, together known as the
nucleocapsid.
▰ Some viruses also have an outer envelope.

Nucleic Acid
8
▰ Viruses have only one type of nucleic acid, either DNA or RNA.
▰ They are classified as DNA viruses and RNA viruses.
▰ Nucleic acid - single or double stranded, circular or linear, segmented or
unsegmented.

Nucleic Acid (Cont..)
9
▰ Most DNA viruses possess dsDNA, except parvoviruses, which have ssDNA.
RNA viruses possess ssRNA, except:
 Reoviruses (e.g. rotaviurs)–possess dsRNA
 Retrovirsues–possess two copies of ssRNA

Capsid
10
▰ Composed of a number of repeated protein subunits (polypeptides) called
capsomeres.
▰ Functions:
 Protects the nucleic acid core from the external environment
 In non-enveloped viruses - initiates the first step of viral replication.
 Antigenic and specific for each virus.

Symmetry
11
▰ Based on arrangement of capsomeres:
Type of symmetry Explanation Examples
Icosahedral (cubical) symmetry  Capsomeres are arranged
as if they lay on the faces
of an icosahedron
 20 triangular facets and 12
corners or vertices
 Rigid structure.
 All DNA viruses
(except poxviruses)
 Most of the RNA
viruses have
icosahedral
symmetry

Symmetry (Cont..)
12
Helical symmetry  Capsomeres are coiled
surrounding the nucleic
acid in the form of a helix
or spiral.
 Flexible structure.
RNA viruses such as-
myxoviruses,
rhabdoviruses,
filoviruses, bunyaviruses,
etc.

Symmetry (Cont..)
13
Complex symmetry  Do not have either of the
above symmetry.
Poxviruses

Envelope
14
▰ Envelope surrounding the nucleocapsid.
▰ Lipoprotein in nature.
 Lipid part is derived from host cell membrane
 Protein part is virus coded, made up of
subunits called peplomers.
 Peplomers - project as spikes on the surface of
the envelope.

Envelope (Cont..)
15
Most Viruses are Enveloped Except:
▰ Non-enveloped DNA viruses - parvovirus, adenovirus and papovavirus
▰ Non-enveloped RNA viruses - picornavirus, reovirus, calicivirus, hepatitis A
virus and hepatitis E virus.

Size of the Viruses
16
▰ Size vary from 20-300nm in size.
▰ Smallest virus - parvovirus(20 nm)
▰ Largest - poxvirus (300nm).
▰ Because of the small size, viruses can pass through bacterial filters and they
cannot be visualized under light microscope.

Size of the Viruses (Cont..)
17

Shapes of the Viruses
18
Most of the animal viruses are roughly spherical with some exceptions:
▰ Rabies virus: Bullet shaped
▰ Ebola virus: Filamentous
▰ Poxvirus: Brick shaped
▰ Adenovirus: Space vehicle shaped
▰ Rotavirus: wheel shaped
▰ Tobacco mosaic virus: Rod shaped

NOMENCLATURE AND
CLASSIFICATION
19

NOMENCLATURE AND CLASSIFICATION
20
Family DNA type Envelope Symmetry Size (nm) Representative Viruses
DNA viruses DNA
Herpesviridae ds,linear Yes Icosahedron 150-200 Herpes simplex virus - 1
Herpes simplex virus- 2
Varicella-zoster virus
Epstein-Barr virus
Cytomegalovirus
Human herpes virus 6,7 & 8
Hepadnaviridae ds, circular,
incomplete
Yes Icosahedron 40–48 Hepatitis B virus
Parvoviridae ss, linear Absent Icosahedron 18–26 Parvovirus B19

NOMENCLATURE AND CLASSIFICATION (Cont..)
21
DNA viruses DNA
Papovaviridae ds, circular Absent Icosahedron 45-55 Human papillomaviruses
JC virus and BK virus
Poxviridae ds, linear Yes Complex 230 x 400 Variola (smallpox)
Molluscum contagiosum virus
Adenoviridae ds, linear Absent Icosahedron 70–90 Human adenoviruses

22
RNA viruses RNA
Picornaviridae ss, +ve sense Absent Icosahedral 28–30 Poliovirus
Coxsackievirus
Echovirus
Enterovirus
Rhinovirus
Hepatitis A virus
Caliciviridae ss, +ve sense Absent Icosahedral 27-40 Norwalk agent
Hepatitis E virus
Togaviridae ss, +ve sense Yes Icosahedral 50-70 Rubella virus
Eastern equine encephalitis virus
Western equine encephalitis virus

23
RNA viruses RNA
Flaviviridae ss, +ve sense Yes Icosahedral (?) 40-60 Yellow fever virus
Dengue virus
St. Louis encephalitis virus
West Nile virus
Hepatitis C virus
Coronaviridae ss, +ve sense Yes Helical 120-160 Coronaviruses
Rhabdoviridae ss, -ve sense Yes Helical 75x180 Rabies virus
Vesicular stomatitis virus
Filoviridae ss, -ve sense Yes Helical 80 x 1000 Marburg virus
Ebola virus

24
RNA viruses RNA
Paramyxoviridae ss, -ve sense Yes Helical 150–300 Parainfluenza virus
Mumps virus
Measles virus
Respiratory syncytial virus
Newcastle disease virus
Metapneumovirus
Orthomyxoviridae ss, -ve sense, 8
segments
Yes Helical 80–120 Influenza viruses- A, B, and C
Bunyaviridae ss, -ve sense,
3 circular
segments
Yes Helical 80–120 Hantavirus
California encephalitis virus
Sandfly fever virus

25
RNA viruses RNA
Arenaviridae ss, -ve sense,
RNA,2 circular
segments
Yes Helical (?) 50-300 Lymphocytic choriomeningitis virus
Lassa fever virus
South American hemorrhagic fever
virus
Reoviridae ds, 10–12
segments
Absent Icosahedral 60-80 Rotavirus
Reovirus
Colorado tick fever virus
Retroviridae 2 identical copies
of +ve sense ss
RNA
Yes Icosahedral
(spherical)
80-110 HTLV (Human T Lymphotropic virus)
HIV (Human immunodeficiency
virus)

VIRAL REPLICATION
27
▰ Viruses undergo a complex way of cell division.
▰ Replication of viruses passes through six sequential steps:
▰ Attachment →Penetration → Uncoating→ Biosynthesis→ Maturation →
Release

28

PATHOGENESIS OF VIRAL
INFECTIONS
29

PATHOGENESIS OF VIRAL INFECTIONS
30
▰ Transmission (entry into the body)
▰ Primary site replication
▰ Spread to secondary site
▰ Manifestations of the disease

Transmission and spread of viruses
31
Mode of transmission Produce Local infection at the portal of entry Spread to distant sites from the portal of entry
Respiratory route
(probably the most common
route)
Produce Respiratory infection-
1. Influenza virus
2. Parainfluenzavirus
3. Respiratory syncytial virus
4. Rhinovirus
5. Adenovirus
6. Coronavirus such as SARS-COV2
7. Herpes simplex virus
Measles virus
Mumps virus
Rubella virus
Varicella-zoster virus
Cytomegalovirus
Parvovirus
Small pox virus
Oral route Produce gastroenteritis
1. Rotavirus
2. Adenovirus-40,41
3. Calicivirus
4. Astrovirus
Poliovirus
Coxsackie virus
Hepatitis Virus – A & E
Cytomegalovirus
Epstein-Barr virus (EBV)

Transmission and spread of viruses (Cont..)
32
Cutaneous route Produce skin lesions
Herpes simplex virus
Human papilloma virus
Molluscumcontagiosum virus
Vector bite - Arboviruses such as-
1. Dengue virus (Aedes)
2. Chikungunya virus(Aedes)
3. Japanese encephalitis virus (Culex)
4. Yellow fever and Zika virus(Aedes)
5. Kyasanur Forest disease virus (Tick)
Animal bite - 1. Rabies virus

33
Sexual route Produce genital lesions-
2. Human papilloma virus
Hepatitis B, C& rarely D
HIV
Blood transfusion - 1. Hepatitis B, C & rarely D
2. HIV
3. Parvovirus
Injection - Hepatitis B, C & rarely D
HIV

34
Transplacental
route
Produce congenital manifestations in fetus
1. Rubella virus
2. Cytomegalovirus (CMV)
4. Varicella-zoster virus
5. Parvovirus
Transmitted through placenta to fetus, without
congenital manifestations
1. Measles virus
2. Mumps virus
3. Hepatitis B virus
4. Hepatitis C virus
5. Hepatitis D virus
6. HIV
Conjunctival route 1. Adenovirus
2. Enterovirus70
3. Coxsackie virus A-24

Virus Shedding
35
Stages Explanation Examples
Portal of entry For those viruses that produce
local infection.
Influenza virus is shed in
respiratory secretions
Blood Viruses that spread through
vector bite or blood transfusion or
needle pricks
Arboviruses, hepatitis B
Near the target tissue /organ Skin, salivary gland and kidney Varicella zoster, mumps,
cytomegalovirus
No shedding Humans are the dead end for
certain viruses infecting CNS,
such as
Rabies.

Manifestations of Viral Infections (Cont..)
36
Clinical Manifestations (Cont..):
▰ Respiratory viruses such as influenza and coronaviruses produce upper and
lower respiratory tract infections
▰ Gastroenteritis may be produced by viruses such as rotavirus and norovirus
▰ Hemorrhagic fever may be a manifestation of viruses such as dengue, Ebola
virus etc
▰ Neurotropic viruses can produce meningitis (enteroviruses) or encephalitis
(rabies, Japanese encephalitis)

Morphological Changes in the Host Cells
37
▰ Certain viruses induce characteristic changes in the host cells (e.g. inclusion
body), which can be detected by histopathological staining.

Inclusion body
38
▰ Aggregates of virions or viral proteins & other products of viral replication that
confer altered staining property to the host cell.
▰ Characteristic of specific viral infections.
▰ They have distinct size, shape, location and staining properties by which they
can be demonstrated in virus infected cells under the light microscope.

Inclusion body (Cont..)
39
Intracytoplasmic inclusion bodies
Negri bodies – seen in Rabies virus
Paschen body- seen in Variola virus
Guarnieri bodies - seen in Vaccinia virus
Bollinger bodies - seen in Fowl pox virus
Molluscum bodies - seen in Molluscum contagiosum virus
Perinuclear cytoplasmic body- seen in Reovirus

Inclusion body (Cont..)
40
Intranuclear inclusion bodies
A)Cowdry type A inclusions
Torres body- seen in Yellow fever
Lipschultz body - seen in Herpes simplex
B)Cowdry type B inclusions - seen in
Poliovirus
Adenovirus
Intracytoplasmic & intranuclear inclusion bodies
Owl’s eye appearance- seen in Cytomegalovirus
Measles

LABORATORY DIAGNOSIS OF
VIRAL DISEASES
41

LABORATORY DIAGNOSIS OF VIRAL DISEASES
(Cont..)
42
Direct Demonstration of Virus
Electron microscopy
Immunoelectron microscopy
Fluorescent microscopy
Light microscopy
Detection of Viral Antigens
By various formats such as ELISA, direct IF, ICT, flow through assays.

(Cont..)
43
Detection of Specific Antibodies
Conventional techniques such as HAI, neutralization test and CFT
Newer diagnostic formats such as ELISA, ICT, flow through assays.
Molecular Methods to Detect Viral Genes
Nucleic acid probe—for detection of DNA or RNA by hybridization
PCR—for DNA detection by amplification
Reverse transcriptase-PCR—for RNA detection
Real time PCR—for DNA quantification
Real time RT-PCR—for RNA quantification.

(Cont..)
44
Isolation of Virus by
Animal inoculation
Embryonated egg inoculation
Tissue cultures: Organ culture, explant culture, cell line culture (primary, secondary and
continuous cell lines).

TREATMENT OF VIRAL
DISEASES
45

TREATMENT OF VIRAL DISEASES
46
Anti-Viral drugs Mechanism of action Active against
Anti-herpesvirus drugs
Acyclovir , Valacyclovir, Penciclovir Inhibit Viral DNA polymerase HSV1>HSV2>VZV&EBV
Famciclovir Inhibit Viral DNA polymerase HSV,VZV,HBV
Ganciclovir Inhibit Viral DNA polymerase CMV,EBV, HSV, VZV
Cidofovir Inhibit Viral DNA polymerase HSV,CMV
Foscarnet Inhibit Viral DNA polymerase HSV& CMV
Fomivirsen Inhibit mRNA of CMV CMV(including resistant strains)
Docosanol (topical) Inhibit the fusion of the human host cell
with envelope of herpes virus
HSV (recurrent herpes labialis)
Trifluridine (topical) Inhibits viral DNA polymerase Herpes keratitis (eye drops)

TREATMENT OF VIRAL DISEASES (Cont..)
47
Anti- Influenza virus drugs
Oseltamivir,
Zanamivir
Neuraminidase Inhibitor H1N1flu
Avian flu
Seasonal flu
Amantadine,
Rimantadine
Matrix protein inhibitor Seasonal flu

TREATMENT OF VIRAL DISEASES (Cont..)
48
Anti-Hepatitis drugs
Telbivudine, tenofovir, lamivudine,
adefovir, entecavir
Nucleoside analogues Primarily for Hepatitis B
Interferon alfa Indirectly inhibits viral protein
synthesis
For hepatitis B and C infection
Grazoprevir Paritaprevir ,
Simeprevir
NS3/4A inhibitors (proteases) For hepatitis C infection
Dasabuvir, Sofosbuvir NS5B inhibitors (polymerases) For hepatitis C infection
Daclatasvir, Ledipasvir, Velpatasvir NS5A inhibitors For hepatitis C infection
Ribavirin Nucleoside inhibitor For For hepatitis C infection

IMMUNOPROPHYLAXIS FOR
VIRAL DISEASES
49

Viral Vaccines (Active Immunization)
50
▰ Since viral antigens are potent immunogens, viral vaccines confer prolonged
and effective immunity.
▰ Vaccines for viral infections may be available either in live, killed or in subunit
forms.

Killed Viral Vaccines
51
▰ Preparation: By inactivating viruses with heat, phenol, formalin or beta
propiolactone. Ultraviolet irradiation is not recommended because of the risk
of multiplicity reactivation. E.g., Rabies vaccine .
▰ Advantages- They are more stable and are safely when given in
immunodeficiency or in pregnancy.
▰ Disadvantages- Killed vaccines are associated with more adverse side effects
due to reactogenicity, which can be reduced to some extent by purification of
viruses.

Subunit Vaccines
52
▰ Only a particular antigen of the virus is incorporated in the subunit vaccine.
▰ Preparation - DNA recombinant technology. The gene coding for the desired
antigen is integrated into bacteria or yeast chromosome. Replication of the
bacteria or yeast yields a large quantity of desired antigens, e.g. Hepatitis B
vaccine
▰ Unlike killed vaccines, there is no local side effects associated with subunit
vaccines

Live Vaccines
53
▰ Preparation- Most of the live vaccines are prepared by attenuation by serial
passages. (Exception is small pox vaccinewhere the naturally occurring
vaccinia viruses were used for vaccination).
▰ Advantage- Live vaccines provide a stronger and long lasting immunity,
mimickingimmunity produced after natural infection. They are administered
as a single dose (except OPV).
▰ Disadvantages- Live vaccines are risky in immunodeficiency or pregnancy.
They are less stable than killed vaccines

Passive Immunization (Immunoglobulin)
54
▰ Passive immunization is indicated when an individual is immunodeficient or
when an early protection is needed (i.e. for post-exposure prophylaxis).
However, as there is no
▰ Passive immunization has no role in prevention of subsequent infections.
▰ Human immunoglobulins are available for many viral infections such as
mumps, measles, hepatitis B, rabies and varicella-zoster.

Combined Immunization
55
▰ Simultaneous administration of vaccine and immunoglobulin in post exposure
prophylaxis is extremely useful. It is recommended for-
 Hepatitis B (neonates born to HBsAg positive mothers or for unvaccinated
people following exposure )
 Rabies (for exposures to severe class III bites)

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