Virology Lecture Notes PDF

Virology Lecture 1 INTRODUCTION Nucleic Acids DNA or deoxyribonucleic acid is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA, most DNA is located in the cell nucleus. The information in DNA is stored as a code made up of four...

Virology Lecture 1 INTRODUCTION Nucleic Acids DNA or deoxyribonucleic acid is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA, most DNA is located in the cell nucleus. The information in DNA is stored as a code made up of four chemical Bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases and more than 99 percent of those bases are the same in all people the order or sequence of these bases determines the information available for building and maintaining an organism similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other A with T and C with G to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule together a base and sugar and phosphate are called a nucleotide, Nucleotides are arranged in two long strands that form a spiral called a double helix. RNA or ribonucleic acid , It is an important molecule with long chains of nucleotides , nucleotide contains a nitrogenous base , ribose sugar and a phosphate just like DNA , RNA is usually single-stranded while DNA is usually double-stranded in addition , RNA contains ribose while DNA contains deoxyribose , Deoxyribose lacks one oxygen atom RNA has the bases Adenine (A), Uracil (U) (instead of thymine in DNA), Cytosine (C) and Guanine (G).  Viruses  Are the smallest unicellular infectious agents (ranging from about 20 nm to about 300 nm in diameter)  contain only one kind of nucleic acid (RNA or DNA) as their genome ,  the nucleic acid is encased in a protein shell which may be surrounded by a lipid-containing membrane , GENERAL PROPERTIES OF VIRUS 1. Viruses are obligate intracellular molecular parasites which are very small and infectious. 2. The virus genome is composed either of DNA or RNA. 3. The virus genome directs the synthesis of virion components within an appropriate host cell. 4. Progeny virus particles spread infection to new cells. VIRUS STRUCTURE Viruses range in size from 20 nanometers in diameter such as the Parvoviridae to several hundred nanometers in length in the case of the filoviridae. All viruses contain a nucleic acid genome RNA or DNA and a protective protein coat called the capsid, the nucleic acid genome plus the protective protein coat is called the nucleocapsid which may have icosahedral or helical or complex symmetry. Viruses may or may not have an envelope, enveloped viruses obtain their envelope by budding through a host cell membrane in some cases the virus buds through the plasma membrane but in other cases the envelope may be derived from internal cell membranes such as those of the Golgi body or the nucleus. Some of the Differences between Bacteria and Viruses are as follows: VIRION NUCLEOCAPSID STRUCTURES 1- Icosahedral symmetry: An icosahedron is a Platonic solid with twenty faces. 2- Helical symmetry: Protein subunits can interact with each other and with the nucleic acid to form a coiled ribbon like structure. 3- Complex symmetry: These are regular structures, but the nature of the symmetry is not fully understood. Classification of Viruses Classical virus classification schemes have been based on the consideration of four major properties of viruses: 1. The type of nucleic acid which is found in the virion (RNA or DNA). 2. The symmetry and shape of the capsid. 3. The presence or absence of an envelope. 4. The size of the virus particle. Viruses can be placed in one of the seven following groups: 1- dsDNA viruses (e.g., Adenoviruses, Herpesviruses and Poxviruses). 2- ssDNA viruses (+ strand or "sense") DNA (e.g. Parvoviruses). 3- dsRNA viruses (e.g. Reoviruses). 4- (+) ssRNA viruses (e.g., Picornaviruses and Togaviruses). 5- (−) ssRNA viruses (e.g., Orthomyxoviruses and Rhabdoviruses). 6- ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses). 7- dsDNA-RT viruses (e.g. Hepadnaviruses). Lecture 2 Virus Replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm. 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 virus replication occurs in seven stages, namely; 1. Attachment 2. Entry, 3. Uncoating, 4. Transcription / mRNA production, 5. Synthesis of virus components, 6. Virion assembly and 7. Release (Liberation Stage). Attachment It is the first step of viral replication. The virus attaches to the cell membrane of the host cell. It then injects its DNA or RNA into the host to initiate infection. In animal cells these viruses get into the cell through the process of endocytosis which works through fusing of the virus and fusing of the viral envelope with the cell membrane of the animal cell and in plant cells it enters through the process of pinocytosis which works on pinching of the viruses. Entry The cell membrane of the host cell invaginates the virus particle, enclosing it in a pinocytotic vacuole. This protects the cell from antibodies like in the case of the HIV virus. Uncoating Cell enzymes (from lysosomes) strip off the virus protein coat. This releases or renders accessible the virus nucleic acid or genome. Transcription / mRNA production For some RNA viruses, the infecting RNA produces messenger RNA (mRNA). This is translation of the genome into protein products. For others with negative stranded RNA and DNA, viruses are produced by transcription then translation. The mRNA is used to instruct the host cell to make virus components. The virus takes advantage of the existing cell structures to replicate itself. Synthesis of virus components The following components are manufactured by the virus using the host's existing organelles:  Viral proteins: Viral mRNA is translated on cellular ribosomes into two types of viral protein: o Structural: proteins which make up the virus particle o Nonstructural: proteins not found in the virus particle, mainly enzymes for virus genome replication  Viral nucleic acid (genome replication): New viral genomes are synthesized; templates are either the parental genome or newly formed complementary strands, in the case of single-stranded genomes. These genomes are made by either a viral polymerase or (in some DNA viruses) a cellular enzyme, particularly in rapidly dividing cells. Virion assembly A virion is simply an active or intact virus particle. In this stage, newly synthesized genome (nucleic acid), and proteins are assembled to form new virus particles. This may take place in the cell's nucleus, cytoplasm, or at plasma membrane for most developed viruses. Release (liberation stage) The viruses, now being mature are released by either sudden rupture of the cell, or gradual extrusion (force out) of enveloped viruses through the cell membrane. The new viruses may invade or attack other cells, or remain dormant in the cell. In the case of bacterial viruses, the release of progeny virions takes place by lysis of the infected bacterium. However, in the case of animal viruses, release usually occurs without cell lysis. Virus Replication Lecture 3 Isolation of Viruses Unlike bacteria, many of which can be grown on an artificial nutrient medium, viruses require a living host cell for replication. Infected host cells (eukaryotic or prokaryotic) can be cultured and grown, and then the growth medium can be harvested as a source of virus. Virions in the liquid medium can be separated from the host cells by either centrifugation or filtration. Filters can physically remove anything present in the solution that is larger than the virions; the viruses can then be collected in the filtrate Cultivation of Viruses Viruses can be grown in vivo (within a whole living organism, plant, or animal) or in vitro (outside a living organism in cells in an artificial environment, such as a test tube, cell culture flask, or agar plate). Bacteriophages can be grown in the presence of a dense layer of bacteria. Animal virus cultivation is important for 1) identification and diagnosis of pathogenic viruses in clinical specimens, 2) production of vaccines, 3) basic research studies. In vivo host sources can be a developing embryo in an embryonated bird’s egg or a whole animal. For example, most of the influenza vaccine manufactured for annual flu vaccination programs is cultured in hens’ eggs. The embryo or host animal serves as an incubator for viral replication. Location within the embryo or host animal is important. Many viruses have a tissue tropism, and must therefore be introduced into a specific site for growth. Within an embryo, target sites include the amniotic cavity, the chorioallantoic membrane, or the yolk sac. Viral infection may damage tissue membranes, producing lesions called pox; disrupt embryonic development; or cause the death of the embryo. Lecture 4 Anti-viral chemotherapy: Unlike viruses, bacteria and protozoans do not rely on host cellular machinery for replication so processes specific to these organisms provide ready targets for the development of antibacterial and antiprotozoal drugs because viruses are obligate intracellular parasites, and antiviral agents must be capable of selectively inhibiting viral functions without damaging the host making the development of such drugs very difficult, another limitation is that many rounds of virus replication occur during the incubation period and the virus has spread before symptoms appear making a drug relatively ineffective. The mechanisms of action vary among antiviral, oftentimes the drug must activate by enzymes in the cell before it can act as an inhibitor of viral replication the most selective drugs are activated by a virus encoded enzyme in the infected cell. Viral Vaccines: The purpose of viral vaccines is to utilize the immune response of the host to prevent viral disease, immunity to viral infection is based on the development of an immune response to specific antigens located on the surface of virus particles or virus-infected cells, for enveloped viruses the important antigens are the surface glycoproteins. There are two types of viral vaccines: 1- Killed-virus vaccines: Inactivated (killed virus) vaccines are made by purifying viral preparation to a certain extent and then inactivating viral infectivity in a way that dose minimal damage to the viral structural proteins, mild formalin treatment is frequently used. Killed virus vaccines prepared from whole virions generally stimulate the development of circulating antibody against the coat proteins of the virus conferring some degree of resistance, advantages of inactivated vaccines are that there is no reversion to virulence by the vaccine virus and that vaccines can be made when no acceptable attenuated virus is available. The disadvantages of this type are: 1- Extreme care is required in their manufacture to make certain that no residual live virulent virus is present in the vaccine. 2- The immunity conferred is often brief & must be boosted. 3- Parenteral administration of killed virus vaccine, even when it stimulates circulating antibody (IgM, IgG) to satisfactory levels. 4- The cell-mediated response to inactivated vaccines is generally poor. 5- Some killed virus vaccines have induced hypersensitivity to subsequent infection. 2- Attenuated Live-virus Vaccines: Live virus vaccines utilize virus mutants that antigenically overlap with wild type virus but are restricted in some step in the pathogenesis of disease, the genetic basis for the attenuation of most viral vaccines is not known as they were selected empirically by serial passages in animals or cell cultures usually from a species different from the nature host, attenuated vaccines have the advantage of acting like the natural infection with regard to their effect on immunity. They multiply in the host and tend to stimulate longer-lasting antibody production to induce a good cell-mediated response and to induce antibody production and resistance at the portal of entry. The disadvantages are: 1- The risk of reversion to greater virulence during multiplication within the vaccines. 2- The storage and limited shelf life of attenuated vaccines present problems. 3- Interference by coinfection with naturally occurring, wild type virus may inhibit replication of the vaccine virus & decrease it effectiveness. Lecture 5 PATHOGENESIS OF VIRAL DISEASES To produce disease viruses must enter a host come in contact with susceptible cells replicate and produce injury. Specific steps involved in viral pathogenesis: A- Entry and primary replication: In order for host infection to occur a virus must first attach to and enter cells of one of the body surfaces (skin, respiratory tract, gastrointestinal tract, urogenital tract or conjunctiva) most viruses enter their host through mucosa of the respiratory or gastrointestinal tract with exception of some viruses that are enter through blood stream (HBV, HIV) viruses usually replicate at the primary site of enter. B- Viral spread: After primary replication at the site of entry, viruses then spread within the host. Mechanisms of viral spread vary but the most common route is via the bloodstream or lymphatic's, the presence of virus in blood is called “viremia”.  C- Cell injury & clinical illness: Destruction of virus-infected cells in the target tissues and physiologic alteration in the host by the tissue injury are partly responsible for the development of diseases. Clinical illness from viral infections is the result of a complex series of events and many of the factors that determine degree of illness are unknown. D- Viral shedding: Viral shedding is the last stage of pathogenesis of viral infection this is a necessary step to maintain a viral infection in populations of hosts, Shedding usually occurs from the body surfaces involved in viral entry shedding occur at different stages of disease depending on the particulate agent involved in some viral infections such as rabies human represent dead-end infections and shedding is not occurred. Genetic of Viruses: DNA viruses: Almost all DNA viruses which infect animals contain double- stranded DNA exceptions include the Parvoviridae (e.g., parvovirus B19, adeno- associated virus) and the Circoviridae (these include the recently discovered TT virus, which may be related to the development of some cases of hepatitis). RNA viruses: Almost all RNA viruses contain single-stranded RNA exceptions include the Reoviridae (e.g., rotaviruses) which contain double-stranded RNA. Other RNA viruses can be broadly subdivided as follows: Viruses with positive strand (+) RNA genomes i.e., genomes of the same polarity as mRNA viruses in this category include picornaviruses and caliciviruses in addition, retroviruses contain two copies of +RNA although they replicate by a unique mechanism. Viruses with negative strand (-) RNA genomes i.e., genomes of opposite polarity to mRNA viruses in this category all have helical capsids. Three members of the class are sufficiently closely related to comprise a distinct taxonomic order: Mononegavirales (Rhabdoviruses, paramyxoviruses and filoviruses). The other (-) strand RNA viruses have segmented genomes (orthomyxoviruses have 8 segments while arenaviruses and bunyaviruses have either two or three segments respectively. The arenaviruses and some bunyaviruses are also unique in that they possess ambience genomes (i.e., their genomes contain both (+) and (-) strand RNAs). Lecture 6 ORTHOMYXOVIRUSES (INFLUENZA VIRUSES) Are major determinant of morbidity and mortality caused by respiratory disease and outbreaks of infection sometimes occurs in worldwide epidemics, three immunological types of Influenza viruses are known designated A, B, (contains human and animal) and C (contains human and swine). Influenza virus particles are usually spherical and about 100 nm in diameter it has negative sense single strand RNA (A and B with 8 separated segments while C has 7 segment of RNA). Influenza virus particle contain 9 different structural proteins it has a lipid envelope derived from the cell surrounds the virus particle. 2 virus-encoded glycoproteins, the hemagglutinin (HA) and neuraminidase (NA) are inserted into the envelope these 2 surface glycoproteins are the important antigens that determine antigenic variation of influenza viruses & host immunity, there are 15 subtype of HA (H1-H15), and 9 subtypes of NA (N1-N9) e.g., H1N1 Swine and H1N5 human. Clinical Finding: Influenza attacks mainly the upper respiratory tract it poses a serious risk for the elderly, the very young, and people with underlying medical conditions such as lung, kidney, or heart problems, diabetes and cancer. Lab. Diagnosis: A- Isolation and identification of virus: Nasal washings, gargles, and throat swabs are the best specimens for viral isolation and should be obtained within 3 days after the onset of symptoms. Classically embryonated eggs and primary monkey kidney cells have been the isolation methods of choice for influenza viruses. B- Serology: Antibodies to several viral proteins (HA, NA) are produced during infection with Influenza virus, the immune response against the HA glycoprotein is associated with resistance to infection. Routine serodiagnostic test in use are based on hemagglutination inhibition (HI) and ELISA (Enzyme Linked Immunosorbent Assay). Neutralization test are the most specific and the best predictor of susceptibility to infection but are more unwieldy and more time-consuming to perform than other tests. ELISA test is more sensitive than other assays. Lecture 7 PARAMYXOVIRUSES & RUBELLA VIRUS The paramyxoviruses include the most important agents of respiratory infectious of infants and young children (parainfluenza virus). The WHO estimates that acute respiratory infections and pneumonia are responsible every year worldwide for the death of 4 million children under 5 years of age, all members of Paramyxoviridae family initiate infection via the respiratory tract, replication of the respiratory pathogens is limited to the respiratory epithelia. The morphology of the paramyxoviridae is pleomorphic with particles 50 nm or more in diameter occasionally ranging up to 700 nm, the envelope seems to be fragile making virus particles labile to storage conditions and prone to distortion in electron micrographs, the viral genome is linear, negative-sense single stranded RNA, non-segmented, about 15 kb in size. Most paramyxoviruses contain six structural proteins, three proteins are complex with viral RNA and three proteins participate in the formation of the viral envelope, the envelope contains viral hemagglutinin (HN) glycoprotein which sometimes carries neuraminidase activity and fusion (F) glycoprotein. Lab. Diagnosis A- Antigen detection: Direct identification of viral antigens in specimens is commonly done, antigens may be detected in exfoliated nasopharyngeal cells by direct or indirect immunofluorescences tests, these methods are rapid but less sensitivity than viral isolation and must be carefully controlled. B- Isolation and identification of virus: Nasal washes are good specimens for viral isolation. Bronchoalveolar lavage fluid and lung tissue have also been used. Primary monkey kidney cells are the most sensitive for isolation of parainfluenza viruses. C- Serology: Antibody can be measures using Neutralization test (Nt), Hemagglutination inhibition (HI), or ELISA test. RUBELLA (GERMAN MEASLES) Is an acute febrile illness characterized by a rash and lymphadenopathy that effects children and young adults. It is the mildest of common viral exanthems however, infection during early pregnancy may result in serious abnormalities of the fetus including congenital malformations and mental retardation the consequences of rubella in utero are referred to as the congenital rubella syndrome. Rubella a member of the Togaviridae family is the sole member of the genus Rubivirus, Rubella is Positive-sense, single strand RNA, non-segmented, not enveloped virus. Lab. Diagnosis Clinical diagnosis of rubella is unreliable because many viral infections produce symptoms similar to those of rubella. A- Isolation and identification of virus: Nasopharyngeal or throat swabs taken 6 days before and after onset of rash are a good source of rubella virus. Various cell lines of monkey or rabbit origin may be used. B- Serology: - The HI test is a standard serologic test for rubella however, serum must be pretreated to remove non-specific inhibitors before testing. ELISA tests are preferred because serum pretreated is not required and they can be adapted to detect specific IgM detection of IgG is evidence of immunity. Lecture 8 ENTERIC VIRUSES & RHINOVIRUSES Enteroviruses are transient inhabitant of the human alimentary tract and may be isolated from throat or lower intestinal tract. Rhinoviruses are isolated chiefly from the nose and throat (common cold virus). Many picornaviruses (enterovirus & rhinovirus) cause diseases in human ranging from severe paralysis to aseptic meningitis, myocarditis, vesicular and exanthematous skin lesion and respiratory illness. The virion of picornaviruses consists of a capsid shell of 60 subunits, each of four proteins (VP1-VP4) arranged with icosahedral symmetry around a genome made up of a linear single strand of Positive sense-RNA, RNA range from 7.2-8.4 kb in size, none enveloped viruses. Poliomyelitis: is an acute infectious disease that in its serious form affects the central nervous system. The destruction of motor neurons in the spinal cord results in flaccid paralysis. Lab. Diagnosis: The virus may be recovered from throat swabs taken soon after onset of illness and from rectal swabs or stool sample collected over long periods, Poliovirus is uncommonly recovered from the cerebrospinal fluid (Nt). Lecture 9 HERPES VIRUSES The herpes virus family contains several of the most important human pathogens, Clinically, the herpes viruses exhibit a spectrum of diseases some have wide host range whereas others have a narrow host-cell range. The outstanding property of herpes viruses is their ability to establish lifelong persistent infections in their hosts and to undergo periodic reactivation. Herpes viruses possess a large number of genes, some of which have proved to be susceptible to antiviral chemotherapy. The herpes viruses that commonly infect humans include herpes simplex virus type 1 & 2 (HSV 1 and 2), Varicella-Zoster (VZ) virus, Epstein-Barr virus (EB), Cytomegalovirus (CMV), human herpesviruses 6 & 7 and herpes virus 8. Herpes B virus of monkeys can also infect humans. All herpes viruses have a core of linear double-strand DNA in the form of toroid surrounded by a protein coat that exhibits icosahedral symmetry and has 162 capsomeres. The nucleic acid is surrounded by an envelope that is derived from the nuclear membrane of the infected cell and contains viral glycoprotein. The base composition of herpes viruses DNAs varies there is little DNA homology among different herpes except for HSV 1 and 2 (50% homology), HV 6 and 7 (30-50% homology). Herpes simplex virus They are responsible for a spectrum of diseases ranging from gingivostomatitis to Keratoconjunctivitis, encephalitis, genital diseases, and infections of newborns HVS establish latent infections in nerve cells recurrences are common. Lab. Diagnosis A- Isolation & identification of viruses: Virus may isolate from herpetic lesion and may also be found in throat washings, CSF, and stool, both during primary infection and during asymptomatic periods. B- PCR & Hybridization: PCR assay can be used to detect virus and are sensitive and specific. PCR amplification of viral DNA from CSF has replaced viral isolation from brain tissue. C- Serology: Antibodies appear in 4-7 days after infection and reach a peak in 2-4 weeks. The diagnostic value of serological assay is limited by the multiply antigens. Cytomegalovirus (CMV) CMV are ubiquitous herpes viruses that are common causes of human disease the name for classic cytomegalic inclusion disease derived from the propensity for massive enlargement of cytomegalovirus infected cells. Cytomegalic inclusion disease is a generalized infection of infants caused by intrauterine or early postnatal infection with CMV. CMV poses an important public health problem because of its high frequency of congenital infections which may lead to severe congenital anomalies.  Virion of CMV Lab. Diagnosis A- PCR & Antigen detection assay: PCR assay are designed to detect replicating virus, blood and urine are most commonly tested, antibodies against viral antigens can be used to detect virus- positive in patients. B- Serology: Detection of IgG antibodies by using ELISA indicative of past infection while detection of viral IgM refer to a current infection. C- Isolation of virus: Human fibroblasts cell culture is used for virus isolation attempts, the virus can be recovered most readily from throat washing and urine. Incubation for 2-3 weeks is needed to appear the cytological changes. Lecture 10 ONCOVIRUSES Viruses are etiologic factors in the development of several types of human tumors including two of great significance world-wide cervical cancer and liver cancer, at least 15% of all human tumors worldwide have a viral cause. The viruses that have been strongly associated with human cancers are human papilloma viruses (genital tumor, squamous cell carcinoma and oropharyngeal carcinoma) EBV (Nasopharyngeal carcinoma and lymphoma), Hepatitis B (Hepatocellular carcinoma), HTL virus (Adult T cell leukemia), AIDS and HCV (Hepatocellular carcinoma). Like other viruses, tumor viruses are classified among different virus families according to the nucleic acid of their genome and the biophysical characteristics of their virion, most recognized tumor viruses have a DNA genome, DNA tumor viruses encode viral oncoproteins that are important for viral replication but also affects cellular growth control pathways, most RNA tumor viruses belong to the retrovirus family, HTL virus & HIV. Multistep Carcinogenesis: carcinogenesis is a multistep process; that is, multiple genetic changes must occur to convert a normal cell into a malignant one. Intermediate stages have been identified and designated by term such as " immortalized", "hyperplastic" and " preneoplastic". Tumors usually develop slowly over a long period of time. the natural history of human and animal cancers suggests a multistep process of cellular evolution, probably involving cellular genetic instability and repeated selection of rare cells with some selective growth advantage. The number of mutations underlying this process is estimated to range from five to eight. observation suggest that activation of multiple cellular oncogenes and inactivation of tumor suppressor genes are involving in the evolution of tumors whether or not a virus is involved. It appears that a tumor virus usually acts as a cofactor, providing only some of the steps required to generate malignant cells. Viruses are necessary-but not sufficient-for development of tumors with a viral etiology. Virus often act as initiators of the neoplastic process and may do so by different mechanisms. Tenets of viral carcinogenesis: 1-Viruses can cause cancer in animal and humans. 2-Tumor viruses frequently establish persistent infections in natural host. 3-Host factors are important determinants of virus-induced tumorigenesis. 4-Viruses are seldom complete carcinogens. 5-Virus infections are more common than virus-related tumor formation. 6-Long latent period usually elapse between initial virus infection and tumor appearances. 7-Viral strains may differ in oncogenic potential. 8-Viruses may be either direct or indirect acting carcinogenic agents. 9-Oncogenic viruses modulate growth control pathways in cells. 10-Animal models may reveal mechanisms of viral carcinogenesis. 11-Viral markers are usually present in tumor cells. 12-One virus may be associated with more than one type of tumor. Human Papillomaviruses (HPV) Papillomaviruses are slightly larger in diameter (55 nm) and contain a large genome 8 kbp (kbp= Kilo-base pair). Papillomaviruses have double-strand and circular DNA and non-enveloped virus, Papillomavirus can cause several different kinds of warts in skin, genital warts, laryngeal papilloma and cervical cancer. Lab. Diagnosis A- PCR assay: Detection of viral DNA by using PCR is the most important diagnostic materials in lab. B- Serology: Detection of IgM in serum indicate of recent infection. Lecture 11 Hepatitis viruses Viral hepatitis is a systemic disease primarily involved liver most cases of acute viral hepatitis in children and adults are caused by one of the following agent : Hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV) , Hepatitis viruses produce acute inflammation of the liver resulting in a clinical illness characterized by fever gastrointestinal symptoms such