Introduction to Virology

[Link]. Murat Sayan

Kocaeli Üniversitesi, Rutin PCR Lab. Sorumlu Öğt.Üyesi
Yakın Doğu Üniversitesi, DESAM Kurucu Öğrt. Üyesi
sayanmurat@[Link] Medical Virology,
0533 6479020 12 Nov 2015.
Contents of Teaching in Medical Virology Lecture:
1. Introduction to virology
2. Laboratory diagnosis
3. Childhood illnesses
4. Human herpesviruses
5. Respiratory infections
6. Gastroenteritis
7. Acute neurological syndromes
8. Hepatitis
9. Human retroviruses
10. Human papillomaviruses
 Introduction
• Viruses contribute significantly
to the global burden of
infectious disease.
• We experience countless
infections throughout their lives,
with particularly high frequency
in early childhood. While most of
these are mild, viruses may cause
severe disease in susceptible
individuals, such as the mal-
nourished, immuno-
compromised, the very old and
the very young.
• Recent years have also seen the
emergence of new viral diseases
such as HIV, SARS and "swine flu"
(H1N1 pandemic influenza A).
 What is a virus?
• They are all cells
Viruses are uniquely • They store their genetic
different from the many uni- information as DNA
cellular micro-organisms you • Within their cell, they
have studied so far. contain all the organelles
Protozoa, yeasts, bacteria, necessary for producing
mycoplasmas, rikettsiae energy and synthesizing
and chlamydiae are all living proteins, carbohydrates,
organisms with the cell wall structures etc.
following features in
common: • Replicate by means of
binary fission
 What is a virus?
• Viruses do not share these • The genome consists of only one type
properties. They are not cells. They of nucleic acid: either RNA or DNA.
are very simple structures consisting • Most DNA viruses are double
essentially of a nucleic acid genome, stranded (ds) and most RNA viruses
protected by a shell of protein. They have a single stranded (ss) genome.
are metabolically inert and can only • A ssRNA genome may be either
replicate once they are inside a host positive sense (this means that it can
cell. be used as mRNA to make proteins)
or negative sense. Negative sense
RNA is complimentary to mRNA, in
other words, it has to be copied into
mRNA. The viral genome codes only
for the few proteins necessary for
replication: some proteins are non-
structural e.g. polymerase and some
are structural, i.e. they form part of
the virion structure.

Polio virus; ssRNA genome

 Terminology
• Virion = virus particle
• Capsid = protein shell which
surrounds and protects the genome.
It is built up of multiple (identical)
protein sub-units called capsomers.
Capsids are either icosahedral or
tubular in shape
• Nucleocapsid = genome plus capsid
• Envelope = lipid membrane which
surrounds some viruses. It is derived
from the plasma membrane of the
host cell.
• Peplomers = proteins found in the
envelope of the virion. They are
usually glycosylated and are thus
more commonly known as
glycoproteins.
Envelop
Viral replication: Viruses are the ultimate parasite. They are totally dependent
on a host cell to replicate (make more copies of itself).
• Genome replication
• Adsorption: The surface of the virion contains Multiple copies of the viral genome are
structures that interact with molecules synthesized by a viral polymerase (one of the
(receptors) on the surface of the host cell. This is "early" proteins).
usually a passive reaction (not requiring energy), • Late phase
but highly specific. It is the specificity of the Transcription and translation of viral mRNA and
reaction between viral protein and host synthesis of the structural ("late") proteins
receptor that defines and limits the host species which are needed to make new virions.
and type of cell that can be infected by a • Assembly of new virions
particular virus. Damage to the binding sites on Assembly of new viral capsids takes place either
the virion or blocking by specific antibodies in the nucleus (e.g. herpesviruses) or in the
(neutralization) can render virions non- cytoplasm (e.g. poliovirus) of the cell, or
infectious. sometimes, just beneath the cell surface (e.g.
• Uptake: The process whereby the virion enters budding viruses such as influenza). The proteins
the cell. It occurs either as a result of fusion of self assemble and a genome enters each new
the viral envelope with the plasma membrane capsid.
of the cell or else by means of endocytosis. • Release of progeny virions
• Uncoating: Once inside the cell, the protein Release of new infectious virions is the final
coat of the virion dissociates and the viral stage of replication. This may occur either by
genome is released into the cytoplasm. budding from plasma membrane or else by
• Early phase disintegration (lysis) of the infected cell. Some
Once the genome is exposed, transcription of viruses use the secretory pathway to exit the
viral mRNA and translation of a number of non- cell: virus particles enclosed in golgi-derived
structural ("early") proteins takes place. The vesicles are released to the outside of the cell
function of these is to replicate the viral when a transport vesicle fuses with the cell
genome. membrane.
Attachment
Endocytosis
Uncoating

Replication
Assembly and maturation
Release of new viruses
 How do viruses cause disease?
• Viruses are capable of infecting all types • Viruses enter the body by inhalation,
of living organism from bacteria to ingestion, sexual intercourse or
humans, (including plants and insects!). A inoculation through the skin or mucous
major factor that controls which cell type membranes. Infection may also
a virus can infect (cell tropism) is the sometimes be passed from a mother to
presence (on the cell surface) of the her foetus transplacentally (vertical
appropriate receptor, to which the virus transmission). Once a virus has gained
must attach in order to gain entry into the entry into the body, infection may either
cell. remain localised to the site of entry (an
example of this is influenza where the
virus remains confined to the respiratory
tract), or it may cause a disseminated
infection. Here, the virus replicates
initially at the site of entry, but then
enters the blood (viraemia) or lymphatics
and spreads throughout the body (e.g.
Measles). Other viruses such as Rabies
and Herpes Simplex may replicate locally
initially, then enter nerve endings and
travel up the axon to infect the central
nervous system.
 How do viruses cause disease?
• The term incubation period defines the • Both viral and host factors contribute to
time from exposure to an organism to the clinical disease during the course of a viral
onset of clinical disease. In general, infection. Host immune cells release
viruses that cause localized infections interferons and other cytokines which
have short incubation periods (<7 days), induce the symptoms of fever and
while in disseminated infections, the malaise. Tissue specific damage may be
incubation period tends to be longer. due to virus-induced lysis of infected cells
or due to inflammation and destruction of
infected cells by the host's immune
response. Because viruses replicate intra-
cellularly, recovery from a viral infection
requires the action of specific cyto-toxic T
lymphocytes which recognise and
eliminate virus-infected cells. Virus-
specific antibody levels rise during the
course of the infection, but antibody plays
only a limited role in recovery from an
established infection for most viruses.
Nonetheless specific antibody plays a very
important role in preventing re-infection
of the host with the same virus.
 How do viruses cause disease?
• An effective immune response can eliminate most viruses from the body and thus most viral
infections are short lived. However, there are certain viruses that are able to evade the immune
response and establish persistent infections in their host.
• The most famous example of such a virus is HIV, but there are many others. Viruses use a variety
of strategies to evade the immune system. On the whole, these persistent infections are
asymptomatic and only manifest clinically if the patient becomes immuno-compromised.
 Viruses and cancer:

• About 15% of human cancers are

caused by viruses. Certain persistent
viruses survive in the host by
transforming the cells they infect
(inducing infected cells to
proliferate). However, the virus
infection is only the first step in the
pathway to malignancy and only a
small percentage of infected people
actually get cancer.
• Common virus-induced cancers
include: carcinoma of the cervix
(Human papillomavirus), liver cancer
(hepatitis B and C), Kaposi sarcoma
(human herpesvirus 8) and Burkitts Human papillomavirus (HPV)
lymphoma (Epstein Bar virus).
Nobel Prize in Physiology or
Medicine 2008
Distribution of cervical cancer due to HPV
 What is a virus?
• They have no
organelles.
• They are very small,
sizes range from 20 to
200 nm. This is beyond
the resolving power of
the light microscope.
Disinfection and inactivation of viruses:

Heat; Most are inactivated at 56 °C for 30 minutes or at 100 °C for a few seconds
Drying Variable; enveloped viruses are rapidly inactivated.
Ultra-violet irradiation; Inactivates viruses
Organic solvents (Chloroform, Ether, Alcohol); Enveloped viruses are inactivated; those
without are resistant.
Oxidizing and reducing agents; Viruses are inactivated by formaldehyde, chlorine,
iodine and hydrogen peroxide
Phenols; Most viruses are resistant