Virology Lecture 2 PDF

Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah Viral replication The viral replication cycle is described below in two different ways: 1. Growth curve, which shows the amount of virus produced at different times after infection. The growth curve in figure be...

Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah Viral replication The viral replication cycle is described below in two different ways: 1. Growth curve, which shows the amount of virus produced at different times after infection. The growth curve in figure below shows that first event is disappearance of the virus as represented by the solid line dropping to the x axis. Although the virus particle is no longer present, the viral nucleic acid continues to function and begins to accumulate within the cell. The time during which no virus is found inside the cell is known as the Eclipse period. Single infected cell may release a large number of daughter virions. The time taken for a single cycle of replication is about 15–30 hours. In a cycle of replication, the virus cannot be demonstrated inside the host cell from the stage of penetration till the appearance of mature daughter virions. This period is known as the eclipse stage. The latent period is defined as the time from the onset of infection to the appearance of the virus extracellularly. At the end of latent period, alterations of cell morophology accompanied by marked derangement of cell function; this is called cytopathic effect (CPE) which culminates in the lysis and death of cells. These CPE can be seen under the light microscope. 1 Page Viral Growth Curve.  Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah 2. Stepwise description of the specific events within the cell during virus growth cycle (Viral Replication): Viruses are obligatory intracellular parasites. They do not possess any machinery which may be of help to them in synthesizing their nucleic acids or proteins the genetic information for which is present in the genome of the virus. The viruses make use of the metabolic machinery of the host cell to undertake these processes. The replication of viruses takes place in a systematic manner and the whole event can be divided into a number of stages (Steps in viral replication): 1. Recognition of the target cell. 2. Attachment of the virus particle to the cell surface. 3. Penetration into the host cells. 4. Uncoating of the virus of its outer layers and capsid. 5. Biosynthesis Transcription of mRNA from viral nucleic acid. Translation of mRNA into “early proteins.” Replication of viral nucleic acid. Synthesis of late proteins. 6. Assembly of virus in the nucleus or cytoplasm. 7. Budding of enveloped viruses. DNA viruses The genome replication of most DNA viruses takes place in the cell's nucleus. except Poxviruses which replicate in the cytoplasm. RNA viruses Replication usually takes place in the cytoplasm. except retroviruses, influenza virus and hepatitis virus which replicate in the nucleus. RNA viruses have a higher mutation rate than DNA viruses 2 Page Viral Structure and replication step flowchart  Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah I-Early events (attachment, penetration, &uncoating) Adsorption (Attachment): It refers to the attachment of a virus to target cells. Virus particles can only infect cells possessing surface “receptors” specific to the particular virus species. For example, CD4 receptor for HIV; ICAM-1 receptor for rhinoviruses, the complement (C3) receptor that is also the receptor for the Epstein-Barr virus. It is the receptors on a cell that determine whether it can be infected by a certain virus (The specify of the attachment determines the host range of the virus). When a virus encounters such a cell, it adsorbs to it either with the capsid or, in enveloped viruses, by means of envelope proteins. Penetration (Entry): Depending on their nature, whether enveloped or nonenveloped, the viruses penetrate into cell by different mechanisms: A nonenveloped virus enters the cell by a process known as endocytosis. The endocytosis is an active process by which nutrients and other molecules are brought into a cell. This process is also known as viropexis. example enterovirus, adenovirus, and rhinovirus. The enveloped viruses enter the cell by an alternate method called fusion, in which the viral envelope fuses with the plasma membrane and releases the capsid into the cell cytoplasm. Human immunodeficiency virus (HIV) is a classic example of an enveloped virus, which enters the host cell by this method. Uncoating (disassembly): Is the process of separation of viral nucleic acid from its protein core. This process apparently varies depending 3 Page With most viruses, the uncoating is accomplished by the action of lysosomal enzymes present inside the phagocytic vacuoles and Golgi vesicles of the host cell. These lysosomal enzymes degrade the protein of the viral capsid. In some other viruses, uncoating is caused exclusively by enzymes present in the host cell cytoplasm. In case of poxvirus, the uncoating is affected by the action of a specific enzyme encoded by the viral DNA, which is synthesized soon after  Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah infection. on the nature of the virus causing infection. II- Middle events (Gene Expression and Genome Replication) 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 mRNA. a. In DNA viruses: mRNA can be formed using the host’s own RNA polymerase to transcribe directly from the viral DNA. e.g., poxviruses b. In RNA viruses: The host polymerases do not work from RNA molecules...therefore they produce their mRNA by several different routes: 1. Double- stranded RNA(In ds RNA viruses): one strand is first transcribed by viral polymerase into mRNA. (The virus carries its own polymerase for transcribing into mRNA). e.g. Reovirus. 2. In ss RNA viruses.... there are three routes to the formation of mRNA: A- Single- stranded RNA of positive polarity: If the ss RNA virus has the same base sequence as that required (+ve sense) ….it can be used directly as mRNA. (These viruses use their RNA genome directly as mRNA) e.g. Poliovirus. 4 Page B- Single- stranded RNA of negative polarity: 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. (An mRNA must be transcribed by using the negative strand as a template. The virus carries its own RNA- dependent RNA polymerase). e.g., Influenza virus.  Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah C- In reverse transcribed RNA (RT): the positive sense ss are first made into a negative sense ss DNA using the viral reverse transcriptase enzyme. (The RNA transcribed into double- stranded DNA by the RNAdependent DNA polymerase (reverse transcriptase), carried by the virus. This DNA copy is then transcribed into viral mRNA by the regular host cell RNA polymerase). e.g. Retroviruses. Viral proteins synthesis (Translation): Once the viral mRNA of either DNA or RNA viruses is synthesized, it is translated by host cell ribosomes in cytoplasm into viral proteins. Some of which are early proteins, i.e. enzymes required for replication of viral 5 Page genome, and others of which are late proteins, i.e. structural proteins of the progeny viruses.  Early proteins: occurring before the replication of the genome.  Late proteins: occurring after genome replication. Late viral mRNA synthesis (transcription) Late viral proteins synthesis (translation): Capsid proteins  Lecture 2 / Virology /7thSemester / Dept. of (MLT) Dr.Sheylan S. Abdullah III- Late events (Assembly and Release) Assembly: viral NA enters into a capsid to be assembled into mature infective virus (virion). Release: Release of the completed viruses is the last step in the replication of viruses. Unenveloped Nonenveloped viruses, however, release through rupture in the host cell plasma membrane. This type of release usually results in the death of the host cell. Enveloped viruses are released by budding through the outer cell membrane Except Herpes virus by budding from the nuclear membrane. Budding does not immediately kill the host cell and in some cases the host cell survives. 6 Page The Growth cycle of virus 30/Sep./2024