The members of this family are enveloped viruses that contain a single stranded RNA genome and three structural proteins. The capsid (C) protein and the viral RNA form the icosahedral nucleocapsid, and the other two proteins are envelope associated. Currently, the family Flaviviridae is divided into three genera: Flavivirus, Hepatitis C virus, and Pestivirus. However, the viruses in the genus Pestivirus (classical swine fever virus and bovine viral diarrhea virus) are only of veterinary interest.

A. Flavivirus

The genus Flavivirus comprises more than sixty viruses. These include many viruses of medical importance, such as yellow fever, St. Louis encephalitis, Japanese encephalitis, dengue fever viruses, and West Nile virus, all of which are mosquito transmitted. Tickborne encephalitis virus is, of course, transmitted by ticks. [Note: Like the viruses in the Alphavirus genus of the family Togaviridae , most of the viruses in this genus are, therefore, arboviruses.] All of the viruses in the genus Flavivirus share a common group antigen.

1. Epidemiology and pathogenesis: As arboviruses, the medically important members of this genus are transmitted to humans by the bite of an infected mosquito or tick. These viruses are maintained in nature by replicating alternately in an arthropod vector and a vertebrate host. Figure 1 shows the global distributions of yellow fever and dengue fever.

Fig1. Global distribution of yellow fever and dengue fever.

2. Replication: Following attachment to the cell surface, the virus is taken up by receptor-mediated endocytosis. Replication of the viral RNA is as described for Type I RNA viruses . Only one species of viral mRNA, the genomic RNA, is found in infected cells. It is translated into a single, long polyprotein, which is processed by virus-coded and cellular proteases, giving rise to three structural and seven nonstructural proteins. Nucleocapsids are formed in the cytoplasm, and maturation of the viral particle occurs by envelopment of the nucleocapsid, not at the plasma membrane as with viruses in the family Togaviridae, but, instead, at cytoplasmic Golgi mem branes. Virus particles then accumulate in vesicles and are extruded when the vesicles move to the cell surface.

3. Clinical significance: Viruses in the genus Flavivirus are associated with several different clinical syndromes. These include: encephalitis (St. Louis encephalitis, Japanese encephalitis, and tickborne encephalitis viruses); hemorrhagic fever (yellow fever virus); and fever, myalgia, and rash (dengue viruses). Although there is little mortality associated with classic dengue fever, in certain parts of the world, such as Southeast Asia, a severe form of dengue infection occurs, particularly in infants and young children. Called dengue hemorrhagic fever or dengue shock syndrome, it is associated with a significant mortality (10 percent or higher) if untreated. Like dengue fever, West Nile fever is a mosquito-trans mitted, acute, usually self-limited illness that presents chiefly with fever, malaise, lymphadenopathy, and rash. Infection may also result in aseptic meningitis or meningoencephalitis, especially in older adults. The first outbreak of West Nile encephalitis in the United States occurred in the New York City area in the summer of 1999. The outbreak was preceded by a significant die-off of wild crows and exotic birds at the Bronx zoo. The West Nile virus, following bird migration, has now spread to all 48 contiguous states in the United States.

4. Laboratory identification: A specific diagnosis is most often made by serologic means (that is, by demonstrating at least a fourfold rise in antibody titer, when comparing acute and convalescent sera). In some cases, virus isolation or demonstration of specific viral antigens is also feasible.

5. Prevention: A safe, highly effective, live attenuated vaccine for yellow fever has been available for many years. In China and Japan, a formalin-inactivated Japanese encephalitis virus vaccine is used, whereas, in central Europe, a formalin-inactivated vaccine is widely used to prevent tickborne encephalitis. Another important method of prevention is vector control. In urban areas, elimination of breeding sites can dramatically reduce the population of Aedes aegypti mosquitoes, which serve as the vector for both yellow fever and dengue viruses.

B. Hepatitis C viruses

Hepatitis C virus (HCV) was discovered in 1988 in the course of searching for the cause of non-A, non-B, transfusion-associated hepatitis. At that time, HCV accounted for 90 percent of the cases of non-A, non-B hepatitis. The hepatitis C viruses are heterogeneous and can be divided into six types on the basis of their nucleotide sequences.

 1. Transmission and pathogenesis: Although HCV was initially identified as a major cause of posttransfusion hepatitis, intravenous drug users and patients on hemodialysis are also at high risk for infection with HCV. Tattooing is also a leading cause of HCV infection. In addition, there is evidence for sexual transmission of HCV as well as for transmission from mother to infant. In the infected individual, viral replication occurs in the hepatocyte and, probably, also in mononuclear cells (lymphocytes and macrophages). Destruction of liver cells may result both from a direct effect of the activities of viral gene products and from the host immune response, including cytotoxic T cells. Although DNA viruses are associated with chronic infection and cancer development, this is not generally the case for RNA viruses. Nonetheless, certain strains of HCV have been associated with hepatocellular carcinoma development, even in the absence of cirrhosis. Particular alleles of the core gene of HCV have been strongly associated with development of hepatocellular carcinoma. Variant core gene alleles have also been associated with interferon-γ (IFN-γ) treatment failures.

2. Clinical significance: The majority of infections with HCV are sub clinical, but about 25 percent of infected individuals present with acute hepatitis, including jaundice (Figure 2). More importantly, a significant proportion of infections progress to chronic hepatitis and cirrhosis. Finally, some of these individuals go on to develop hepatocellular carcinoma many years after the primary infection.

Fig2. Natural history of infection with hepatitis C virus.

 3. Laboratory identification: A specific diagnosis can be made by demonstration of antibodies that react with a combination of recombinant viral proteins. Sensitive tests are also now available for detection of the viral nucleic acid by RT-PCR (reverse transcription of the viral RNA followed by polymerase chain reaction to amplify the DNA copy).

4. Treatment and prevention: Tests to screen blood for HCV have been available for several years, so that HCV as a cause of transfusion-associated hepatitis is now unusual. Treatment of patients with chronic hepatitis by IFN-γ is sometimes beneficial but, in most cases, only for the period during which the patient is receiving the IFN-γ. Treatment with IFN-γ plus ribavirin provides a significantly improved response, and combination therapy is the treatment of choice (Figure 3). Chronic hepatitis resulting in severe liver damage may be an indication for a liver transplant. Figure 4 summarizes hepatitis A, B, and C.

Fig3. Combination treatment with interferon and ribavirin for chronic hepatitis C. [Note: Patients receiving ribavirin alone showed a biologic and histologic response, but no decrease in circulating hepatitis C virus.]

Fig4. Summary of hepatitis A, B, and C.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم شؤون المعارف ينظم دورة متقدمة في تحقيق المخطوطات لملاكاته

قسم الشؤون الفكرية يصدر العدد العشرين من مجلة دراسات إفريقية

المجمَع العلمي يكرم الأساتذة المشاركين في مشروع الدورات القرآنية الصيفية في كربلاء

العتبة العباسية المقدسة تختتم فعاليات البرنامج المركزي الأسبوعي لمنتسبيها

المزيد

الآخبار الصحية

تحذير من "عدوى بكتيرية" تسبب نوبات قلبية

ماذا يحصل لجسمك عند التوقف عن استخدام الزيت في الطهي؟

الأمل في كبسولة.. "فيتامين شهير" يبطئ التقدم في العمر

اشتهاء أطعمة بشكل مفاجئ.. ناقوس خطر للسرطان ؟!

المزيد

الآخبار التكنلوجية

زلزال أفغانستان يحصد أكثر من ألف قتيل.. ويدمر آلاف المنازل !

ناجٍٍ وحيد من انزلاق أرضي.. دمّر قرية سودانية بأكملها !

نهر الفرات.. مورد مائي بين الندرة والتقاسم

ما السر وراء مشية إيلون ماسك الغريبة والسريعة ؟

المزيد

مواضيع ذات صلة

Pathogenesis and clinical significance of HIV

Transmission of HIV

HIV replication

Hepatitis D

Prevention and Treatment of hepatitis B

Differentiating Acute and Chronic Hepatitis and the Chronic Carrier State

Togaviridae

Caliciviridae

Picornaviridae

Laboratory Assays of Hepatitis B

Epidemiology of Hepatitis B

Hepatitis A