Virus Classification and Replication 2024 PDF

Virus Classification and Virus Replication Lec-2- Dr. Shnyar Hamid  VIRUS CLASSIFICATION AND TAXONOMY One classification scheme was developed in the 1970s by Nobel laureate David Baltimore. The Baltimore classification system categorizes viruse...

Virus Classification and Virus Replication Lec-2- Dr. Shnyar Hamid  VIRUS CLASSIFICATION AND TAXONOMY One classification scheme was developed in the 1970s by Nobel laureate David Baltimore. The Baltimore classification system categorizes viruses based on the type of nucleic acid genome and replication strategy of the virus. Positive-strand (also positive-sense or plus-strand) RNA is able to be immediately translated into proteins; as such, messenger RNA (mRNA) in the cell is positive strand. Negative-strand (also negative-sense or minus- strand) RNA is not translatable into proteins; it first has to be transcribed into positive-strand RNA. Viruses are only classified using order, family, genus, and species (Table 1)  Table 1 Taxa Used to Classify Viruses Taxon Notes Example Order § Ends in -virales suffix; only about half of viruses are Picornavirales currently classified in orders. Family § Ends in -viridae suffix; sub- families are indicated with - Picornaviridae virinae suffix. Genus § Ends in -virus suffix. Enterovirus Species § Generally the “common name” of the virus. Classifying Rhinovirus A (Serotypes and cataloging anything below the species classification. include Human rhinovirus 1, which includes strains human rhino- virus 1A and human rhinovirus 1B) Figure1 Taxa of viruses that infect vertebrates. Viruses are categorized based upon their type of nucleic acid (DNA viruses in yellow boxes and RNA viruses in blue boxes)  Name Origins of Viruses Viruses named after the clinical conditions they cause Human immunodeficiency virus (HIV) Causes the decline of the immune system, leading to immunodeficiency Hepatitis virus; All hepatitis viruses cause liver inflammation (hepatitis) Poxviruses; From pockes meaning “sac,” referring to the blistery rash observed Rabies virus From Latin rabies, meaning “madness,” describing the symptoms seen with disease progression Viruses named after their properties Coronavirus From Latin corona, meaning crown, referring to the crown-like appearance of the virions when viewed with an electron microscope Herpesviruses From Greek herpein, “to creep,” referring to the lesions that slowly spread across the skin Viruses named after their location of discovery Ebola virus Named after the Ebola River in northern Democratic Republic of the Congo (formerly Zaire), where the virus first emerged in 1976. Viruses named after people Epstein–Barr virus Named after Michael Anthony Epstein and Yvonne Barr, who discovered the virus Virus Replication  A virus must undergo the process of replication to create new, infectious virions. After gaining entry into the body, a virus makes physical contact with and crosses the plasma membrane of a target cell. Inside, it releases and replicates its genome while facilitating the manufacture of its proteins by host ribosomes. Virus particles are assembled from these newly synthesized biological molecules and become infectious virions. Finally, the virions are released from the cell to continue the process of infection. The seven stages of virus replication are categorized as follows: 1. Attachment 2. Penetration 3. Uncoating 4. Replication 5. Assembly 6. Maturation 7. Release  1. ATTACHMENT Virus attachment—the binding of the virus to the host cell. This interaction is specific: the virus contains a virus attachment protein that adsorbs to a cell surface receptor on the cell (Table 2). 1- Rhinovirus binds a protein known as intercellular adhesion molecule 1 (ICAM-1), involved in the attachment of one cell to another. 2- Influenza A virus strains bind to the sialic acid sugars found at the ends of cellular carbohydrate chains (Fig.2). 3- Coreceptors; HIV initially binds to a protein known as CD4 on the surface of T lymphocytes with one of two coreceptor proteins (CCR5 and CXCR4).  Figure 2 Cell surface receptors Different viruses use specific cell surface receptors for attachment. Virus Cell surface receptor(s) Intercellular adhesion molecule 1 (ICAM-1) (90%), low-density Rhinoviruses lipoprotein receptor (10%) Poliovirus Poliovirus receptor (PVR) CD155 Human immunodeficiency CD4 (receptor); CCR5 or CXCR4 (coreceptors) virus Influenza A virus Sialic acid Measles virus CD46, CD150 Herpes simplex virus-1 Heparan sulfate, HVEM, Nectin-1 Dengue virus DC-SIGN Hepatitis B virus Sodium taurocholate– cotransporting polypeptide Human papillomavirus Heparan sulfate, integrins  2. PENETRATION Penetration refers to the crossing of the plasma membrane by the virus, following attachment. Enveloped and nonenveloped viruses 1. Receptor- mediated endocytosis a) Most types of viruses use clathrin-mediated endocytosis to enter the cell, including dengue virus, and hepatitis C virus (Fig 3).. b) papillomaviruses (that cause warts or cervical cancer), use caveolae-mediated endocytosis.  2. PENETRATION 2. Other forms of endocytosis, such as: -Bulk-phase endocytosis, the cell forms a vesicle that engulfs whatever molecules are present in the extracellular fluid, including viruses. -Phagocytosis is a form of receptor-mediated endocytosis that is used by specialized cells to engulf entire cells. Large DNA viruses, Herpes simplex virus type 1 (HSV-1). penetration method of enveloped viruses by fusion. Fusion of the viral envelope can occur at the cell membrane or within endocytosed vesicles, such as the endosome Is mediated by the same viral protein that is used by the virus for attachment or by a different viral protein, depending upon the virus. Fig.3 Viral penetration into the cell. Different viruses take advantage of various cellular mechanisms to gain entry into the cell. Table 3 Methods of Penetration for Select Human Viruses Type of penetration (entry) Virus examples Dengue virus, hepatitis C virus, reovirus, Clathrin-mediated endocytosis adenovirus. Caveolin-mediated endocytosis Human papillomavirus, hepatitis B virus HIV, influenza, respiratory syncytial virus, Fusion herpes simplex viruses, dengue virus, Ebola virus  3. UNCOATING Refers to the breakdown or removal of the capsid, causing the release of the virus genome into the cell (fig.4) Can be separated from or tightly linked with penetration. 1. Rhinoviruses are taken into the cell by receptor-mediated endocytosis in clathrin-coated vesicles. Within the acidic endosome, the virus expands in size about 4%, and one of the capsid proteins, VP1 (viral protein 1), forms pores in the endosome that allow the release of the rhinovirus RNA genome.  3. UNCOATING 2. Poliovirus; they have been thought to not enter the cell at all, the binding of the poliovirus capsid to the cell surface receptor causes a conformational change in the virion that creates a pore in the cell membrane through which the viral RNA is released into the cytoplasm. Figure 4 Uncoating of virion capsids 4. REPLICATION Virus’s genome acts as the instructions for the synthesis of virus proteins. Virus genome is copied by replication protein synthesis create new virion’s particles The replication strategy of a virus is generally dependent upon the type of nucleic acid genome it contains. 4. REPLICATION The Baltimore classification system categorizes the viruses into seven classes based upon their type of genome: 1. Double-stranded DNA viruses 2. Single-stranded DNA viruses 3. Double-stranded RNA viruses 4. Positive-sense RNA viruses 5. Negative-sense RNA viruses 6. RNA viruses that reverse transcribe 7. DNA viruses that reverse transcribe TABLE 4 Families of Human Viruses Within Each Replication Class Family Virus examples Class I: dsDNA viruses Adenoviridae Adenovirus Herpesviridae Herpes simplex virus, Epstein–Barr virus, varicella zoster virus Poxviridae Variola, vaccinia Class II: ssDNA viruses Parvoviridae Parvovirus B19 Class III: dsRNA viruses Reoviridae Rotavirus Class IV: +ssRNA viruses Coronaviridae Human coronavirus Hepeviridae Hepatitis E virus Picornaviridae Poliovirus, rhinovirus, enterovirus, hepatitis A virus Class V: −ssRNA viruses Filoviridae Ebola virus, Marburg virus Orthomyxoviridae Influenza A virus, influenza B virus Paramyxoviridae Nipah virus, Hendra virus, measles virus, mumps virus Rhabdoviridae Rabies virus Class VI: RNA viruses that reverse transcribe Retroviridae Human immunodeficiency virus-1 and -2 Class VII: DNA viruses that reverse transcribe Hepadnaviridae Hepatitis B virus  Viruses with dsDNA genomes have similar nucleic acid to living organisms and often use the enzymes and proteins that the cell normally uses including its DNA polymerases and RNA polymerases; are located in the nucleus. So all dsDNA viruses that infect humans enter the nucleus of the cell, while RNA genomes do not. During replication, the ssDNA genome enters the nucleus of the host cell, where the ssDNA is converted to dsDNA by DNA polymerase. dsRNA viruses contain an RdRp that is carried into the cell within the virion. § The genomes of +ssRNA viruses are infectious, since positive-sense RNA is able to be directly translated by ribosomes. § −ssRNA viruses are not infectious and must be transcribed into vmRNA before translation can occur. § Therefore, −ssRNA viruses must also carry an RNA- dependent RNA polymerase (RdRp) into the cell. § Retroviruses are viruses that reverse transcribe an RNA genome into cDNA. § Reverse transcriptase (RT) is the enzyme that carries this out and has the activity of an RNA- dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H. § Transcription and genome replication is carried out by host enzymes.  Hepatitis B virus is also a retroid virus but instead reverse transcribes in order to create its DNA genome, which is partially single-stranded and partially double- stranded and known as rcDNA. This is repaired to a completely double-stranded episome (cccDNA) in the nucleus of the cell. RNA polymerase II transcribes an RNA pregenome that is reverse transcribed, after being packaged into the capsid, into the rcDNA genome. 4. REPLICATION Viral nucleic acids are found in a variety of configurations. They can be linear or circular, and they can be segmented into several smaller pieces within the virion, as occurs with influenza viruses, or nonsegmented like rabies virus, containing one molecule of nucleic acid that encodes all necessary genes. Regardless of the structure of their nucleic acid, all viruses need to express their viral proteins and replicate their genome within the cell in order to create new virions. § New strains of virus can occur when two different strains infect one cell. § Recombination occurs when the genome of an RNA virus is being replicated and the RdRp jumps from the template of one strain to the template of the other strain, creating a hybrid genome. § Reassortment occurs when the genome segments of segmented viruses are mixed while being packaged into new capsids.  5. ASSEMBLY Viruses components must be collected at a particular site of the cell and undergo assembly to form an immature virus particle, it can take place within the nucleus of the cell, at the plasma membrane, or at a variety of intracellular membranes, such as the Golgi complex. 1. Most nonenveloped DNA viruses assemble their nucleocapsid in the nucleus, since that is the site of genome replication. 2. Viruses with envelopes derived from the plasma membrane usually assemble there.  6. MATURATION Maturation refers to the final changes within an immature virion. Structural capsid changes are often involved Example; influenza HA protein (involved in attachment to the cell’s sialic acid). HA protein must be cleaved into two portions by cell proteases; HA1 and HA2 to become infectious HA1 portion binds the cell surface receptor, the HA2 portion is what fuses the viral envelope to the endosomal membrane to release the virus into the cytoplasm. 7. RELEASE Final step First: for enveloped virus 1. Viruses that obtain their envelope from the plasma membrane generally assemble on the inside layer of the plasma membrane; The plasma membrane is completely wrapped around the virus, which leaves the cell. This process is known as budding (Figure 6). 2. Viruses can bud from any of the membrane systems within the cell, including the rER, Golgi complex, or even the nuclear envelope. Then, undergoes exocytosis to leave the cell. 7. RELEASE Second: for Nonenveloped viruses can also exit the cell via exocytosis. Lytic viruses, however, disrupt the plasma membrane and cause the lysis, or bursting, of the cell. This releases the nascent virions to infect new cells. Many nonenveloped human viruses are released through cell lysis. Figure 6 Virion budding. (A) Rubella virus virions are observed budding from the host plasma membrane in this transmission electron micrograph. (B)helical Ebolavirus virions (blue) are budding from an infected cell (yellow).