1
Virus Growth Cycle : Replication
The steps in viral infection are
1
Attachment
2
Penetration
3
Uncoating
4
Gene expression and Synthesis of viral components
5
Assembly
6
Release
General Steps in Viral Replication Cycle
After the synthesis of viral nucleic acid and viral proteins,
the components assemble to form new infectious virions
(from modest numbers to more than 100,000 particles)
during (from 6–8 hours (picornaviruses) to more than 40
hours (some
herpesviruses)).
Abortive infections fail to produce infectious progeny,
either
because the cell may be nonpermissive and unable
to support the expression of all viral genes or because the
infecting virus may be defective, lacking some functional
viral gene.
A latent infection may produce, with the persistence of
viral genomes, the expression of no or a few viral genes,
and the
survival of the infected cell. In other cases, the metabolic
processes of the host cell are not altered significantly,
although the cell synthesizes viral proteins and nucleic
acids, and the cell is not killed.
Replication of Viruses: An Overview
Viruses multiply only in living cells. The host cell must
provide the energy and synthetic machinery and the
low-molecular-weight precursors for the synthesis of
viral proteins and nucleic acids. The viral nucleic acid
carries the genetic specificity to code for all the virus-
specific macromolecules in a highly organized fashion.
Soon after interaction with a host cell, the infecting virion is
disrupted and its measurable infectivity is lost. This phase
of the growth cycle is called the eclipse period; followed
by an interval of rapid accumulation of infectious progeny
virus particles. In some cases, as soon as the viral nucleic
acid enters the host cell, the cellular metabolism is
redirected exclusively toward the synthesis of new virus
particles and the cell will be destroyed.
HIV
Membrane of
white blood cell
HIV entering a cell
0.25 µm
New HIV leaving a cell
The reproductive cycle of HIV, the retrovirus that causes AIDS
Attachment) Adsorption( interaction of a virion with a
specific receptors
generally glycoproteins
on the
surface of a cell. In some cases the virus binds
protein
sequences
(eg,
picornaviruses)
and
in
others
oligosaccharides
(eg,
orthomyxoviruses
and
paramyxoviruses
).For example,
▪
HIV virus binds to the CD4 receptor on cells of the
immune system,
▪
rhinoviruses bind ICAM-1,
▪
Epstein-Barr virus recognizes the CD21 receptor on B
cells.
Not all cells in a susceptible host will express the necessary
receptors; for example, poliovirus is able to attach only to
cells in the central nervous system and intestinal tract of
primates. Each susceptible cell may contain up to 100,000
receptor sites for a given virus. The attachment step may
initiate irreversible structural changes in the virion.
Attachment
VIRAL
LIFE
CYCLE
ATTACHMENT
PENETRATION
HOST
FUNCTION
S
ASSEMBLY
(MATURATION)
Transcription
REPLICATION
RELEAS
E
UNCOATING
Translation
MULTIPLICATION
2- Penetration or
Entry...
:
After binding,the cell
membrane invaginates around the adsorped virus
particle, the virus particle is then engulfed by the
cell. In some systems, this is accomplished by
receptor-mediated endocytosis, with uptake of the
ingested virus particles within endosomes. There
are also examples of direct penetration of virus
particles across of or fusion of the virion envelope
with the plasma membrane.
3
-
Uncoating occurs shortly after penetration.
The protein coat of virus is removed by the
host cell enzymes. After that, the genome
may
be
released
as
free
nucleic
acid
(picornaviruses)
or
as
a
nucleocapsid
(reoviruses).
The infectivity of the parental
virus is lost at the uncoating stage
.
The essential point in viral replication is that specific
mRNAs must be transcribed from the viral nucleic acid
for successful expression and duplication of genetic
information. Once this accomplished, viruses use cell
components to translate the mRNA
4- Gene expression and synthesis of viral
components
In DNA viruses,
mRNA can be formed using the
host’s own RNA polymerase to transcribe directly
from the viral DNA.
In RNA viruses,
the host polymerase does not work
from RNA molecules...therefore they produce their
mRNA by several different routes:
1- In ds RNA viruses:one strand is first transcribed
by viral polymerase into mRNA.
2- In ss RNA viruses....there are three routes to the
formation of mRNA:
A- If the ss RNA virus has the same base
sequence as that required (+ve sense(….it can be
used directly as mRNA.
Once viral mRNA has been formed, translation occurs
in the host cytoplasm using host ribosome to synthesize
viral proteins......At this phase, the virus components
appear as separate NA and a separate protein coats.
C- In reverse transcribed RNA (RT,( the positive sense
ss is first made into a negative sense ss DNA using the
viral reverse transcriptase enzyme.
B-If the strand has not the same base sequence as that
required for translation (-ve sense(…it must be
transcribed into a positive sense strand which can then
act as mRNA.
5- Assembly: viral NA enters into a capsid to be
assembled into mature infective virus (virion(
6- Release: the virus is released from the cell
either in a dramatic burst (poliovirus(
Or in a steady stream from the cell structure
(Herpesvirus and myxovirus(
lecture 3
16
Morphogenesis and Release
Newly synthesized viral genomes and capsid polypeptides
assemble together to form progeny viruses.
In general, non enveloped viruses accumulate in infected
cells, and the cells eventually lyse and release the virus
particles.
Enveloped viruses mature by a budding process. Virus-
specific envelope glycoproteins are inserted into cellular
membranes; viral nucleocapsids then bud through the
membrane at these modified sites and in so doing acquire
an envelope.
Enveloped viruses are not infectious until they have
acquired their envelopes.
Therefore, infectious progeny
virions typically do not accumulate within the infected cell
Excess amounts of viral components may accumulate
and be involved in the formation of inclusion bodies in
the cell. As a result of the profound deleterious effects
of viral replication,
cellular cytopathic effects eventually
develop and the cell dies. Virus-induced mechanisms
may regulate apoptosis, Programmed Cell Death
that
makes cells undergo self-destruction.
Some virus infections delay early apoptosis, which
allows time for the production of high yields of progeny
virus. Additionally, some viruses
actively induce
apoptosis at late stages which would facilitate spread of
progeny virus to new cells.
Transmission of Viruses
Different viruses have evolved ingenious and often
complicated mechanisms for survival in nature and
transmission from one host to the next
.
Viruses may be transmitted in the following ways
:
(1)
Direct transmission from person to person by contact. The major means of
transmission may be by
A droplet or aerosol infection
(eg, influenza, measles, smallpox);
►
B fecal-oral route (
eg, enteroviruses, rotaviruses, infectious hepatitis A
)
;
►
C sexual contact
(eg, hepatitis B, herpes simplex type 2, human
immunodeficiency virus)
;
►
D hand-mouth, hand-eye, or mouth-mouth contact
(eg, herpes simplex,
rhinovirus, Epstein-Barr virus)
; -
►
E transfusion of contaminated blood (eg,
hepatitis B, human immunodeficiency
virus)
.
(
2
)
Transmission from animal to animal, with human an
accidental host. Spread may be by bite
(rabies)
or by droplet or
aerosol infection from rodent-contaminated quarters
(eg,
arenaviruses, hantaviruses)
.
(
3
)
Transmission by means of an arthropod vector
(togaviruses,
flaviviruses, and bunyaviruses)
.
Emerging Viral Diseases
Combinations of factors contribute to disease emergence
include:
(1) Environmental changes
(deforestation, damming or other
changes in water ecosystems, flood or drought, famine or
starvation).
(2) Human behavior
(sexual behavior, drug use, outdoor
recreation)
.
(3) Socioeconomic and demographic phenomena
(war,
poverty, population growth and migration, urban decay).
(4) Travel and commerce
(highways, international air travel).
(5) Food production (
globalization of food supplies, changes
in methods of food processing and packaging).
(6) Health care
(new medical devices, blood transfusions,
organ and tissue transplant.
(
7
)
Microbial adaptation
(changes in virulence, development
of drug resistance, cofactors in chronic diseases)
.
(
8
)
Public health measures
(inadequate sanitation and
vector control measures, lack of trained personnel in
sufficient numbers)
.
Examples of emerging viral infections in different regions of
the world include
Ebola virus, Nipah virus, hantavirus
pulmonary disease, HIV infection, dengue hemorrhagic .
fever, West Nile virus, Rift Valley fever
xenotransplantation of nonhuman primate and porcine
organs is considered a potential accidental introduction of
new viral pathogens from the donor species into humans
.
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