Virus Growth Cycle : Replication virology lec.4
General Steps in Viral Replication Cycle
The steps in viral infection are
Attachment
Penetration
Uncoating
Gene expression and Synthesis of viral components
Assembly
Release
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.
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
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.
4- Gene expression and synthesis of viral components
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 mRNAIn 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:
If the ss RNA virus has the same base sequence as that required (+ve sense(….it can be used directly as mRNA.
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.
In reverse transcribed RNA (RT,( the positive sense ss is first made into a negative sense ss DNA using the viral reverse transcriptase enzyme.
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.
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(
Note: Best Answer: In virology, the genome of a RNA virus can be said to be either positive-sense, also known as a "plus-strand", or negative-sense, also known as a "minus-strand". In most cases, the terms sense and strand are used interchangeably, making such terms as positive-strand equivalent to positive-sense, and plus-strand equivalent to plus-sense. Whether a virus is positive-sense or negative-sense can be used as a basis for classifiying viruses. Positive-sense Positive-sense (5' to 3') viral RNA signifies that a particular viral RNA sequence may be directly translated into the desired viral proteins. Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered viral mRNA, and can be immediately translated by the host cell. Unlike negative-sense RNA, positive-sense RNA is of the same sense as mRNA. Some viruses (e.g. Coronaviridae) have positive-sense genomes which can act as mRNA and be used directly to synthesise proteins without the help of a complementary RNA intermediate. Because of this, these viruses do not need to have an RNA transcriptase packaged into the virion. Negative-sense Negative-sense (3' to 5') viral RNA is complementary to the viral mRNA and thus must be converted to positive-sense RNA by an RNA polymerase prior to translation. Negative-sense RNA (like DNA) has a nucleotide sequence complementary to the mRNA that it encodes. Like DNA, this RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA which acts as an mRNA. Some viruses (Influenza, for example) have negative-sense genomes and so must carry an RNA polymerase inside the virion.
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
droplet or aerosol infection (eg, influenza, measles, smallpox);
fecal-oral route (eg, enteroviruses, rotaviruses, infectious hepatitis A);
sexual contact (eg, hepatitis B, herpes simplex type 2, human immunodeficiency virus);
hand-mouth, hand-eye, or mouth-mouth contact (eg, herpes simplex, rhinovirus, Epstein-Barr virus);
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.
