CHAPTER IINTRODUCTIONA. BACKGROUNDAvirusis a smallinfectious agentthatreplicatesonly inside the livingcellsof otherorganisms.Viruses can infect all types oflife forms, fromanimalsandplantstomicroorganisms, includingbacteriaandarchaea.Virus particles (known asvirions) consist of two or three parts: i) thegenetic materialmade from eitherDNAorRNA, longmoleculesthat carry genetic information; ii) aproteincoat that protects these genes; and in some cases iii) anenvelopeoflipidsthat surrounds the protein coat when they are outside a cell. The shapes of viruses range from simplehelicalandicosahedralforms to more complex structures. The average virus is about one one-hundredth the size of the average bacterium. Most viruses are too small to be seen directly with anoptical microscope.One of the viruses can causes diseases for living thing is Poxvirus. Poxviruses are very large for viruses, and are complex. The outer envelope of the virus consists of two layers: the thicker outer layer containing surface tubules or short filaments of helically wound protein subunits (and typically with a hollow channel running through the centre of each tubule) and the thinner inner layer (which is possibly a lipid bilayer - it is known that part of the envelope consists of a lipid bilayer membrane). Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among animal viruses in several respects. First, owing to the cytoplasmic site of virus replication, the virus encodes many enzymes required either for macromolecular precursor pool regulation or for biosynthetic processes.Based on thats issue, this paper will be description all about Poxvirus, like proverties of poxvirus, structure and composition of Poxvirus, classification of Poxvirus, replication of Poxvirus, Poxvirus pathogenesis, prevention and control of poxvirus disease and Poxvirus bibliography.

B. PROBLEMS FORMULATION1. How does the proverties of Poxvirus.?2. How does the structure and composition of Poxvirus.?3. How does the classification of Poxvirus.?4. How does the replicaton of Poxvirus.?5. How does the proces of pathogenesis occur in Poxvirus.?6. How the prevention and control of Poxvirus diseases.?7. How does the Bibliography of Poxvirus.?

C. PURPOSES1. To understand the proverties of Poxvirus.2. To understand the structure and composition of Poxvirus.3. To know the classification of Poxvirus.4. To explain the proces replication of Poxvirus.5. To understand the pathogenesis of Poxvirus.6. To explain the prevention and control of Poxvirus diseases.7. To understand the bibiolography of Poxvirus.

D. ADVENTAGES1. As reference for students about Poxvirus.2. As reference for prevention and control about Poxvirus diseases.

CHAPTER IIDISCUSSION

A. Properties of PoxvirusThe family of poxviridae is divided into 6 genera, with species within each genera closely related. Poxviruses are the largest viruses known dsDNA enveloped virus, bricked shaped virions 200-250 250-300 nm in diameter. 2 morphological forms are seen: M (mulberry) and C (capsule) forms that are interconvertable. Internally, poxviruses have a biconcave "nucleoid" and 2 lateral bodies. Inside the cell, the virion often has a double membrane. The lateral bodies contain various enzymes essential for virus replication. >100 polypeptides have been demonstrated in vaccinia. Poxviruses are very easy to isolate and will grow in a variety of cell cultures and will produce pocks on the chick chorioallantoic membrane (CAM).

B. Structure and Composition1. Sturcture of PoxvirusPoxviruses are very large for viruses, and are complex. The outer envelope of the virus consists of two layers: the thicker outer layer containing surface tubules or short filaments of helically wound protein subunits (and typically with a hollow channel running through the centre of each tubule) and the thinner inner layer (which is possibly a lipid bilayer it is known that part of the envelope consists of a lipid bilayer membrane). The surface tubules are short in Vaccinia (an Orthopoxvirus), but in Orf virus (a Parapoxvirus) they form continuous helices that wind around the virus. In some poxviruses the tubules are replaced by globular protein structures. In Variola an Orthopoxvirus), the tubules are anchored in the outer envelope layer at one end and project from the virus surface as flexible virovilli (these have also been reported for Vaccinia).Inside the envelope is the core and two lateral bodies. The core consists of the core wall - an outer thick palisade layer, 17 nm thick (so called because it is striated, giving the appearance of many tiny columns) and the thinner, smooth inner layer or core membrane, 8 nm thick. Inside the core wall, the core is packed with fibrillar material (the core fibrils) which surrounds the nucleoprotein coil. The nucleoprotein is a continuous helix/cylinder which traverses the length of the virus three times (forming the three so-called 'triplet elements' seen in cross-section) such that three segments run parallel to one-another, but the whole is a continuous tube about 250 nm long).The nucleoprotein consists of the tightly-packed linear double-stranded DNA (dsDNA) genome coated by at least 4 different types of proteins, maintaining the DNA in a superhelical state. A DNA-dependent RNA polymerase is also present in the nucleoprotein or core. This structure is the helical part of the virus, and suggests that poxviruses may have evolved from helical viruses by the addition of extra structures. The poxvirus genome is large, 150 to 300 kbp (kbp = thousand base-pairs), contains no introns (see Adenovirus) and contains more than 150 open reading frames that do not overlap (ORFs - regions of the DNA that are transcribed and so code for potential 'structural' genes, that is genes other than those that control other genes). This is a lot of genes for a virus! The genome ends are palindromic tandem repeats (meaning that they consist of short sequences of bases repeated several times which read the same forwards and backwards, e.g. ATATA). The whole structure depicted above may be enclosed in a cell envelope - a bilayer phospholipid membrane acquired from the host cell, with embedded globular viral glycoproteins.

2. Composition of PoxvirusPoxviruses are large, enveloped, double-stranded DNA viruses, the majority of which possess over 200 genes. Large-scale DNA sequencing projects have provided a wealth of information regarding poxvirus genomes. Poxviruses express three temporal classes of genes, denoted early, intermediate, and late, and some authors have suggested that the early class of genes can be further subdivided into early and immediate-early genes. Mature poxvirus virions lack the symmetry features common to other viruses, such as an obvious helical or icosahedral capsid architecture; however, studies have shown that early in the assembly of vaccinia virus (VACV), spherical immature virions are produced from trimers of the D13 protein, which forms a honeycomb lattice structure, suggesting that the infectious form of the ancestor of poxviruses may have had an icosahedral capsid.There are four infectious forms of poxvirus virions, the intracellular mature virus (IMV), the intracellular enveloped virus, the cell-associated extracellular enveloped virus, and the extracellular enveloped virus, all of which share the same IMV at their center, which contains one membrane, a concave brick core, and protein-based lateral bodies. Recently, an alternative nomenclature was proposed, designating the IMV as mature virions (MVs), designating the intracellular enveloped virus as wrapped virions (WVs), and referring to both the cell-associated extracellular enveloped virus and the extracellular enveloped virus as extracellular virions (EVs).

C. ClassificationThe poxviruses (family Poxviridae) are a family of double-stranded DNA (dsDNA) viruses with very large genomes (130360 kb in length), usually encoding more than 150 genes per genome. The Poxviridae are divided into two subfamilies: Entomopoxvirinae, infecting insects; and Chordopoxvirinae, infecting vertebrates. All human pox viruses are in the Chordopoxovirinae subfamily, and most of them belong to either the Orthopoxvirus (variola, vaccinia, cow pox) or the Parapoxvirus (Orf virus) genus. The chicken pox virus does not belong to this family. Other poxvirus :

1) Monkeypox Monkeypox was first isolated from monkeys in 1958, but it was not until 1970 that it was associated with human disease. To date, over 400 cases have been investigated, mainly from Zaire. The pathogenesis and clinical features for monkeypox is the same as for smallpox. The main differences are a greater degree of lymphadenopathy and a lower capacity for case-to-case spread. Most cases occur in unvaccinated children. The mortality in human monkeypox is appreciable, being in the order of 10%. The management of human monkeypox is the same as for smallpox. Human monkeypox has not been detected outside West Africa. Although monkeypox was first isolated from monkeys, there is no evidence that African monkeys act as the reservoir. The most likely candidate for reservoir is the African squirrel. One important difference between human monkeypox and smallpox is the lower capacity for human spread. The attack rate among unvaccinated contacts is 9% in contrast to >37% for smallpox. Laboratory workers studying monkeypox should be vaccinated. 2) Vaccinia Vaccination with vaccinia was associated with certain risks. Complications ranged from mild reactions and fatal encephalitis. The overall incidence of complications was around 1/800 although the more severe forms occurred only in 15 per million vaccinees. Recent interest has focused on the possible usage of vaccinia as a vector for immunization against other viruses. It is possible that certain changes can be made to the vaccinia genome which makes it less likely to develop side effects. 3) Cowpox Cowpox is a relatively unimportant zoonosis which has only been isolated in Britain and Europe. Infection has been described in humans, cows and cats. Infection in humans usually remain localized, often producing a lesion which is similar to that caused by vaccination, although the inflammatory response is greater and general constitutional symptoms such as fever and myalgia may be present in some cases. In humans, lesions are usually restricted to the hands, but may also be transferred to the face. EM is generally used for the diagnosis of infection. The virus will also grow well on CAM. Human cowpox usually respond to treatment with antivaccinia immunoglobulin, but its use should be restricted to the most severe cases. Although cowpox was first isolated form cattle and farm workers. There is no evidence that cattle serve as the reservoir. In fact, cowpox is very rare in cattle. It has been suggested that the reservoir is actually a small rodent but this is not proven. 4) Parapoxviruses Parapoxvirus infections are widespread in sheep, goats and cattle and relatively unimportant but common human infections occur. Infections in cattle and humans are usually referred to as pseudocowpox, paravaccinia or milker's nodes. Those in sheep and goats as orf. The viruses are closely related and the nomenclature of the human disease is based on the identity of the host form which the infection was acquired. (orf from sheep and pseudocowpox from cattle). Infection occurs via small cuts and abrasions in all hosts and is usually localized. Although the lesions are similar to the early lesions of cowpox and vaccinia, true macrovesicles do not form. In humans, lesions usually occur on the hand but may be transferred to the face. The laboratory diagnosis is usually made by EM. The virus may also be isolated in human, bovine and ovine cells but such investigations are not part of routine diagnostic virology. Parapoxvirus infections occur worldwide, and are of considerable importance. A survey carried in New Zealand showed that 1.4% of workers in the meat industry became infected in 1 year. The lesions are surprisingly painless and thus there is probably substantial under-reporting. Idoxuridine had occasionally been prescribed for treatment but no trials have been carried out to prove the efficacy of treatment. Prevention of human infection is difficult. Reasonable precautions should be undertaken when handling infected animals. 5) Molluscum ContagiosumMolluscum contagiosum is a specifically human disease of worldwide distribution. The incubation period varies from 1 week to 6 months. The lesion begins as a small papule and gradually grows into a discrete, waxy, smooth, dome-shaped, pearly or flesh-coloured nodule. Usually 1-20 lesions but occasionally they may be present in hundreds. In children, the lesions are found on the trunk and the proximal extremities. In adults they tend to occur on the trunk, pubic area and thighs. Individual lesions persist for about 2 months, but the disease usually lasts 6 to 9 months. Constitutional disturbance is rare. The disease occurs world-wide and is spread by direct contact or fomites. In general it tends to occur in children. The disease by may transmitted from skin to skin after sexual intercourse. A diagnosis can usually be made on clinical appearance alone. The diagnosis can be supported by EM. Unlike other poxviruses, molluscum have not been demonstrated to grow in cell culture. Infection is usually benign and painless, with spontaneous recovery in most cases. Where treatment is required for cosmetic reasons, various procedures are available such as curretage, cryotherapy with liquid nitrogen, silver nitrate etc. which are routinely used for the removal of warts. 6) Tanapox Tanapox is a poxvirus infection first recognized in 1957 in the Tana River area of Kenya. It is a zoonosis, human cases have only been seen in the Tana valley and Zaire. The distribution of the virus and the real extent of the human infection is not known, as is the method of transmission of infection. The virus produces a mild febrile illness with one or two skin lesions. The virus does not grow in CAM but will grow in a variety of cell lines. D. Replication Occurs in the cytoplasm - the virus is sufficiently complex to have acquired all the functions necessary for genome replication. There is some contribution from the cell but it is not clear what this is - poxvirus gene expression and genome replication occur in enucleated cells, but maturation is blocked. Phase of replication begin from virus entry to host cell Virus entry to host cellIntracellular mature virion (IMV) particles bind to unknown receptor(s) and fuse with the cell membrane. Extracellular enveloped virion (EEV) particles bind to unknown receptor(s) and are endocytosed into the cell. Initial UncoatingThe viral core particle (CORE) containing the viral genome, the viral DNA-dependent RNA polymerase, and other enzymes is released into the cytoplasm. Early TranscriptionEarly genes (including those coding for immunomodulatory proteins, enzymes, and replication and transcription factors) are transcribed and translated immediately upon core particle entry into the cytoplasm of the cell. TranslocationThe viral core particle translocates to the outside of the cell nucleus. Secondary UncoatingThe viral nucleoprotein (NP) complex, which contains the viral genome, is released. At this point the viral genome is replicated as a concatemer and transcription and translation of intermediate genes (mainly coding for transcription factors) occurs. Late TranscriptionThe viral late genes (coding for structural proteins, enzymes, and transcription factors) are transcribed and translated. AssemblyConcatemeric intermediates are resolved into linear double-stranded DNA and packaged with late viral proteins into immature virions (IV). ReleaseIVs mature into IMVs via an undescribed mechanism which may include processing of the IV through the Golgi apparatus. The IMVs are transported to the periphery of the cell where they are released in one of three ways. IMVs released via cell lysis remain IMVs. Alternatively, IMVs can bud through to the cell surface, picking up a viral envelope from the cell plasma membrane. On the surface cell-associated enveloped virions (CEVs) are pushed via an actin tail into contact with a second cell. Lastly the IMV can bud through the plasma membrane picking up an envelope and becoming an EEV. E. PathogenesisPoxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among animal viruses in several respects. First, owing to the cytoplasmic site of virus replication, the virus encodes many enzymes required either for macromolecular precursor pool regulation or for biosynthetic processes. Second, these viruses have a very complex morphogenesis, which involves the de novo synthesis of virus-specific membranes and inclusion bodies. Third, and perhaps most surprising of all, the genomes of these viruses encode many proteins which interact with host processes at both the cellular and systemic levels. For example, a viral homolog of epidermal growth factor is active in vaccinia virus infections of cultured cells, rabbits, and mice. At least five virus proteins with homology to the serine protease inhibitor family have been identified and one, a 38-kDa protein encoded by cowpox virus, is thought to block a host pathway for generating a chemotactic substance. Finally, a protein which has homology with complement components interferes with the activation of the classical complement pathway. Poxviruses infect their hosts by all possible routes: through the skin by mechanical means (e.g., molluscum contagiosum infections of humans), via the respiratory tract (e.g., variola virus infections of humans), or by the oral route (e.g., ectromelia virus infection of the mouse). Poxvirus infections, in general, are acute, with no strong evidence for latent, persistent, or chronic infections. They can be localized or systemic. Ectromelia virus infection of the laboratory mouse can be systemic but inapparent with no mortality and little morbidity, or highly lethal with death in 10 days. On the other hand, molluscum contagiosum virus replicates only in the stratum spinosum of the human epidermis, with little or no involvement of the dermis, and does not spread systemically from the site of infection. The host response to infection is progressive and multifactorial. Early in the infection process, interferons, the alternative pathway of complement activation, inflammatory cells, and natural killer cells may contribute to slowing the spread of the infection. The cell-mediated response involving learned cytotoxic T lymphocytes and delayed-type hypersensitivity components appears to be the most important in recovery from infection. A significant role for specific antiviral antibody and antibody-dependent cell-mediated cytotoxicity has yet to be demonstrated in recovery from a primary infection, but these responses are thought to be important in preventing reinfection.

F. Prevention and Control1) PreventionThe virus is commonly picked up by inhaling droplets from the mouth and nose of an infected person. It may also be transmitted through contact with material from the skin lesions that appear on an infected individual. The incubation period for smallpox is between seven and 17 days following exposure, with the average being 12 days. The following are the most common symptoms of smallpox. However, each individual may experience symptoms differently. Symptoms may include: Initial symptoms: high fever fatigue head and back aches a distinct rash that presents with the following characteristics, most often, two to three days after exposure: a rash starts with flat, red lesions, usually on the face, arms, and legs lesions become pus-filled and start to crust over early in the second week scabs form which then separate and fall off after three to four weeks A person with smallpox is infectious from the first appearance of fever until all the scabs fall off. There are two chief forms of the disease, variola major and variola minor, and they result in similar lesions. Variola minor follows a milder course, with a fatality rate under 1 percent. Variola major kills an estimated 30 percent of those infected. There is no specific treatment for smallpox. Administering smallpox vaccine to people soon after they are exposed to the virus, however, may prevent the disease from developing or at least ameliorate its effects. Researchers are exploring the potential use of antiviral drugs against smallpox.In 1967 the WHO launched a worldwide vaccination campaign against smallpox; at the time, some 10 to 15 million cases of the disease occurred each year, with more than 2 million deaths. By mid-1975, when all of India was declared free of smallpox, only a few cases were left in two countries, Bangladesh and Ethiopia. In 1979, after two years without a reported case of naturally occurring smallpox, a commission of scientists certified the disappearance of the disease from the earth. The WHO subsequently recommended that countries stop vaccinating against the disease and that laboratory stocks of the virus be destroyed. Underlining the importance of this last request was the death of an English woman in 1979 from smallpox contracted from a laboratory working with the virus. June 1999 was set as the deadline for the destruction of the two known remaining stocks of smallpox virus, kept in guarded freezers at the Centers for Disease Control and Prevention in Atlanta, Ga., and the Russian State Research Center of Virology and Biotechnology in Koltsovo, near Novosibirsk, Siberia. Some scientists, however, argued that the two official stocks should be preserved for research on the virus and on new vaccines and antiviral agents, a position that gained added force from the possibility that additional samples of the virus might exist elsewhere. The WHO accordingly changed the target date for destruction of the virus to 2002. In May 2002, reflecting heightened concerns over the possible use of bioweapons by political extremists, the WHO again put off the elimination of the official stocks.Vaccination was almost universally adopted worldwide around 1800, but it took a major commitment from the WHO in 1965 to achieve eradication.Eradication of smallpox was possible for 3 reasons: There is no other reservoir for VV but man. VV causes only acute infections, from which the infected person either Dies Recovers with life-long immunity. Vaccinia virus is an effective immunogen.

2) ControlControl of the common human poxvirus infections depends on knowledge of their epidemiology. In particular, persons caring for sick livestock should take precautions, but the extent of occupational exposure is such that infection and reinfection are inevitable. Control of infections such as cowpox which has an unknown reservoir, is virtually impossible. Person-to-person transmission is reduced by improving hygiene. Monkeypox is a special case. The World Health Organization considers that the benefits of vaccination do not outweigh the risks and expense. Control of this disease depends on health education and on breaking the link with the animal reservoir; this last should be achieved by the use of forest land near villages for agriculture.In conclusion, it is significant that the strategies used for smallpox eradication are being assessed for the control and eradication of other diseases such as measles and that smallpox recombinant poxviruses may play an important role in the control of other infections.

CHAPTER IIICLOSING1. ConclusionBased on the problems formulation and description, we can conclude :1. Poxviruses are the largest viruses known dsDNA enveloped virus, bricked shaped virions 200-250 250-300 nm in diameter. 2 morphological forms are seen: M (mulberry) and C (capsule) forms that are interconvertable.2. The outer envelope of the virus consists of two layers: the thicker outer layer (and typically with a hollow channel running through the centre of each tubule) and the thinner inner layer (which is possibly a lipid bilayer it is known that part of the envelope consists of a lipid bilayer membrane).3. The Poxviridae are divided into two subfamilies: Entomopoxvirinae, infecting insects; and Chordopoxvirinae, infecting vertebrates.4. Phase replication of Poxvirus is begin from virus entry to host cell, Initial uncoating,early transcription, translocation, secondary uncoating, late transcription, assembly, release.5. The virus is commonly picked up by inhaling droplets from the mouth and nose of an infected person. It may also be transmitted through contact with material from the skin lesions that appear on an infected individual.6. There is no specific treatment for smallpox. Administering smallpox vaccine to people soon after they are exposed to the virus, however, may prevent the disease from developing or at least ameliorate its effects.7. Control of the common human poxvirus infections depends on knowledge of their epidemiology. 8. Control of infections such as cowpox which has an unknown reservoir, is virtually impossible. Person-to-person transmission is reduced by improving hygiene.9. Control of this disease depends on health education and on breaking the link with the animal reservoir; this last should be achieved by the use of forest land near villages for agriculture.

2. Suggestion-BIBLIOGRAPHYAnonymous. 2014. All About Poxviruidae. Accses from http://www. All about Viruses Poxviridae.html. At 11 April 2015.Anonymous. 2013. Poxviruse. Accses from http://www. Poxviruses, Smallpox Virus, Monkey Pox Virus, Molluscum Contagiosum.html. Anonymous. 2009. Poxvirus Composition. Accses from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786582/ At 10 April 2015. Anonymous. 2015. Poxvirus Medical Microbiology. Accses from http://www.ncbi.nlm.nih.gov/books/NBK8364/ At 12 April 2015.Anonymous. 2009. Replication of Poxvirus. Accses from http://virology-microbiology-b.blogspot.com/2009/01/poxviridae.html. At 10 April 2015.Anoymous. 2015. Structure Of Poxvirus. Accses from http://cronodon.com/BioTech/Poxvirus.html. At 9 April 2015.R M, Buller and G, J Palumbo. Poxvirus Pathogenesis. Accses from http://www.Microbiological Reviews / Poxvirus Pathogenesis.html. At 13 April 2015.

Poxvirus, Microbiology IIPage 1