Virus replication

1.  In order to survive, viruses must be able to do the
following:
◦ 1. Find a host cell it can replicate in
◦ 2. Bind to that cell
◦ 3. Enter the cell
◦ 4. Release its genome in order to replicate
◦ 5. Replicate its genome
◦ 6. Transcribe and translate its viral proteins
◦ 7. Package its genome and proteins
◦ 8. Escape from the cell

2. In order to survive, viruses must be able to do the
following:
1. Find a host cell it can replicate in
2. Bind to that cell
3. Enter the cell
4. Release its genome in order to replicate
5. Replicate its genome
6. Transcribe and translate its viral proteins
7. Package its genome and proteins
8. Escape from the cell

3. As viruses are obligate intracellular
pathogens they cannot replicate without
the machinery and metabolism of a host
cell. Although the replicative life cycle of
viruses differs greatly between species and
category of virus, there are six basic stages
that are essential for viral replication.
1. Attachment: Viral proteins on the
capsid or phospholipid envelope interact
with specific receptors on the host cellular
surface. This specificity determines the
host range (tropism) of a virus.
Virus Life Cycle

4. Pathways of virus entry into cells. (A)
Enveloped viruses can bind to cell surface
receptors and directly fuse with the plasma
membrane. Virus particles can also be
internalized via endocytosis, with escape to the
cytosol occurring either from the (B) early
endosome or (C) late endosome and lysosome.
The acidic environment and proteolytic
enzymes in these compartments are required
for fusion and cytosol entry by different
viruses.
2. Penetration: The process of attachment to a
specific receptor can induce conformational
changes in viral capsid proteins, or the lipid
envelope, that results in the fusion of viral and
cellular membranes. Some DNA viruses can
also enter the host cell through receptor-
mediated endocytosis.

5. 3. Uncoating: The viral capsid is removed
and degraded by viral enzymes or host
enzymes releasing the viral genomic
nucleic acid.
Methods for viral genome release into
host cells. (A) Certain viruses, including
rhinoviruses, expand to form pores in the
endosome through which the viral genome
can escape. (B) Influenza and other viruses
induce fusion of the virion envelope with the
endosomal membrane, releasing the viral
genome. (C) Many viruses, including
reoviruses, maintain a partially intact capsid
in the cytosol that acts as a “home base” for
replication.

6. 4. Replication: After the viral genome has been uncoated, transcription or translation
of the viral genome is initiated. It is this stage of viral replication that differs greatly
between DNA and RNA viruses and viruses with opposite nucleic acid polarity. This
process culminates in the de novo synthesis of viral proteins and genome.
Several viruses must transport their
genomes into the nucleus for viral
transcription or replication to
occur. Influenza genome segments are
transported through the nuclear pore
into the nucleus. Herpesvirus capsids
are transported along microtubules to
the nuclear pore, where uncoating
occurs. Adenovirus capsids disassemble
at the nuclear pore, and the viral DNA is
transported into the nucleus. Other
viruses, including hepatitis B virus, are
small enough that the entire capsid may
pass through the nuclear pore.

7. 6. Virion release: There are two
methods of viral release: lysis or
budding. Lysis results in the death of an
infected host cell, these types of viruses
are referred to as cytolytic. An example
is variola major also known as smallpox.
Enveloped viruses, such as influenza A
virus, are typically released from the
host cell by budding. It is this process
that results in the acquisition of the viral
phospholipid envelope. These types of
virus do not usually kill the infected cell
and are termed cytopathic viruses.
Nucleocapsid formation and formation of mature virions. After the
production viral structural proteins, nucleocapsids are assembled in the
cytoplasm and followed by budding into the lumen of the endoplasmic
reticulum (ER)–Golgi intermediate compartment. Virions are then
released from the infected cell through exocytosis.

8.  Semliki Forest Virus is an
enveloped Alphavirus
 When present, symptoms
include headache, fever,
myalgia and athrolgia
 It has 2 transmembrane
proteins (E1 and E2) in its
envelope
 The virus binds to the cellular
receptor, endocytosed, and
fuses with the endosome
membrane to release its
nucleocapsid for replication

9.  Poliovirus is a non enveloped
virus in the Picornavirus family
 It differs from SFV in that when
it binds to its cellular receptor, it
goes through a conformational
change.
 This conformational change may
facilitate the release of genome
into the cell for replication
 Also releases from the cell by
lysis instead of budding

10.  Infection with various picornaviruses may be
asymptomatic or may cause clinical
syndromes such as aseptic meningitis (the
most common acute viral disease of the
CNS), encephalitis, the common cold, febrile
rash illnesses (hand-foot-and-mouth disease),
conjunctivitis, herpangina, myositis and
myocarditis, and hepatitis.
 Picornaviruses shield their receptor binding
site in a region called the canyon in order to
protect it from antibodies.
 Must be conserved so that the virus can bind
to the correct cell in order to replicate.
 HRV16 + ICAM-1 interaction was one of the
first to be studied through cryo
 Was believed that the binding site for ICAM-
1 was located in the canyon region of HRV16

11.  Rotavirus is a genus of viruses that
belong to the family Reoviridae.
Rotaviruses are non-enveloped viruses
that have a double-stranded RNA
genome. They cause gastro-enteritis in
humans and many vertebrates.
 VP4 of rotavirus is important to the
viral life cycle
 It is a determinant of virulence, has
hemagglutination activity and is also a
neutralization site
 The reconstruction showed that VP4
extends from the surface of the virus,
which may then be able to bind to the
cellular receptor more easily

12. Thank you