انت هنا الان : شبكة جامعة بابل > موقع الكلية > نظام التعليم الالكتروني > مشاهدة المحاضرة

Herpes virus

الكلية كلية الصيدلة القسم فرع البايولوجي المرحلة 2
أستاذ المادة سماح احمد كاظم الجبوري 4/10/2011 7:01:28 AM

Herpesviridae

introduction
The herpes virus family contains several of the most important human pathogens. Clinically, the herpes viruses exhibit a spectrum of diseases. Some have a wide host-cell 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. Their frequent reactivation in immunosuppressed patients causes serious health complications. Curiously, the reactivated infection may be clinically quite different from the disease caused by the primary infection.

Properties of Herpes viruses

Important properties of herpes viruses are summarized in Table 1.

Table 1. Important Properties of Herpes viruses.

Virion: Spherical, 150–200 nm in diameter (icosahedral)

Genome: Double-stranded DNA, linear, 125–240 kbp, reiterated sequences

Proteins: More than 35 proteins in virion

Envelope: Contains viral glycoproteins, Fc receptors

Replication: Nucleus, bud from nuclear membrane

Outstanding characteristics:

  Encode many enzymes

  Establish latent infections Latent infections are those in which the virus persists in an occult (hidden or cryptic) form most of the time. Viral sequences may be detectable by molecular techniques in tissues harboring latent infections. Inapparent or subclinical infections are those that give no overt sign of their presence.while Chronic infections are those in which replicating virus can be continuously detected, often at low levels; mild or no clinical symptoms may be eviden.

  Persist indefinitely in infected hosts

  Frequently reactivated in immunosuppressed hosts

  Some are cancer-causing

Classification

Classification of the numerous members of the herpes virus family is complicated. A useful division into subfamilies is based on biologic properties of the agents (Table 2). Alphaherpes viruses are fast-growing, cytolytic viruses that tend to establish latent infections in neurons; herpes simplex virus (genus Simplexvirus) and varicella-zoster virus (genus Varicellovirus) are members. Betaherpes viruses are slow-growing and may be cytomegalic (massive enlargements of infected cells) and become latent in secretory glands and kidneys; cytomegalovirus is classified in the Cytomegalovirus genus. Also included here, in the genus Roseolovirus, are human herpesviruses 6 and 7; by biologic criteria, they are more like gammaherpes viruses because they infect lymphocytes (T lymphotropic), but molecular analyses of their genomes reveal that they are more closely related to the betaherpes viruses. Gammaherpes viruses, exemplified by Epstein-Barr virus (genus Lymphocryptovirus), infect and become latent in lymphoid cells. The Kaposi s sarcoma-associated herpesvirus, designated as human herpesvirus 8, is classified in the Rhadinovirus genus.

Table 2. Classification of Human Herpes viruses.

Type	Synonym	Subfamily	Primary Target Cell	Pathophysiology	Site of Latency	Means of Spread
HHV-1	Herpes simplex virus-1 (HSV-1)	? (Alpha)	Mucoepithelial	Oral and/or genital herpes (predominantly orofacial), as well as other herpes simplex infections	Neuron	Close contact
HHV-2	Herpes simplex virus-2 (HSV-2)	?	Mucoepithelial	Oral and/or genital herpes (predominantly genital), as well as other herpes simplex infections	Neuron	Close contact (sexually transmitted disease)
HHV-3	Varicella zoster virus (VZV)	?	Mucoepithelial	Chickenpox and shingles	Neuron	Respiratory and close contact
HHV-4/EBV	Epstein-Barr virus (EBV), lymphocryptovirus	? (Gamma)	B cells and epithelial cells	Infectious mononucleosis, Burkitt s lymphoma, CNS lymphoma in AIDS patients, post-transplant lymphoproliferative syndrome (PTLD), nasopharyngeal carcinoma, HIV-associated hairy leukoplakia	B cell	Close contact, transfusions, tissue transplant, and congenital
HHV-5	Cytomegalovirus (CMV)	? (Beta)	Monocyte, lymphocyte, and epithelial cells	Infectious mononucleosis-like syndrome,^[9]^retinitis^{, etc.}	^{Monocyte, lymphocyte,}	^{^Saliva}
^HHV-6	^{^Roseolovirus^{, Herpes lymphotropic virus}}	^?	^{^{T cells}}	^{Sixth disease (^{roseola infantum}^{or exanthem subitum)}} (	^{T cells}	^{Respiratory and close contact}
^HHV-7	^{^Roseolovirus}	^?	^{T cells}	^{Sixth disease (^{roseola infantum}^{or exanthem subitum)}} (	^{T cells and}
^HHV-8	^{^{Kaposi s sarcoma-associated herpesvirus}^{(KSHV), a type of}^rhadinovirus}	^?	^{Lymphocyte and other cells}	^{^{Kaposi s sarcoma}^,^{primary effusion lymphoma}^{, some types of multicentric}^{Castleman s disease}}	^{B cell}	^{Close contact (sexual), saliva}

^{Herpesviruses of other animals
In addition to the herpes viruses considered ^endemic^{in humans, some viruses associated primarily with animals may infect humans. These are}^zoonotic^infections:}

^{Zoonotic Herpesviruses}
^Species	^Type	^Synonym	^Subfamily	^{Human Pathophysiology}
^{^{Macaque monkey}}	^CeHV-1	^{Cercopithecine herpesvirus-1, (^{Monkey B virus}⁾}	^?	^{Very unusual, with only approximately 25 human cases reported. Untreated infection is often deadly; sixteen of the 25 cases resulted in fatal ^{encephalomyelitis}^{. At least four cases resulted in survival with severe neurologic impairment. Symptom awareness and early treatment are important for laboratory workers facing exposure.}^[}
^{^Mouse}	^MuHV-4	^{Murine gammaherpesvirus-68 (MHV-68)}	^?	^{^Zoonotic^{infection found in 4.5% of general population and more common in laboratory workers handling infected mice. ELISA tests show factor-of-four (x4)}^{false positive}^{results, due to antibody cross-reaction with other Herpes viruses.}}

^{Herpes virus life-cycle
The replication cycle of herpes virus is summarized as following :
The virus enters the cell by fusion with the cell membrane after binding to specific cellular receptors via envelope glycoproteins. Several herpes viruses bind to cell surface glycosaminoglycans, principally heparan sulfate. Virus attachment also involves binding to one of several coreceptors (eg, members of the immunoglobulin superfamily). After fusion, the capsid is transported through the cytoplasm to a nuclear pore; uncoating occurs; and the DNA becomes associated with the nucleus. The viral DNA forms a circle immediately upon release from the capsid. Viral DNA is transcribed throughout the replicative cycle by cellular RNA polymerase II but with the participation of viral factors. Viral DNA is synthesized by a rolling-circle mechanism. Herpesviruses differ from other nuclear DNA viruses in that they encode a large number of enzymes involved in DNA synthesis. (These enzymes are good targets for antiviral drugs.) Newly synthesized viral DNA is packaged into preformed empty nucleocapsids in the cell nucleus.
Maturation occurs by budding of nucleocapsids through the altered inner nuclear membrane. Enveloped virus particles are then transported by vesicular movement to the surface of the cell.
The length of the replication cycle varies from about 18 hours for herpes simplex virus to over 70 hours for cytomegalovirus. Cells productively infected with herpesviruses are invariably killed. Host macromolecular synthesis is shut off early in infection; normal cellular DNA and protein synthesis virtually stop as viral replication begins.
Immune system evasions
Herpesviruses are known for their ability to establish lifelong infections. One way this is possible is through immune evasion. Herpesviruses have found many different ways to evade the immune system. One such way is by encoding a protein mimicking human ^{interleukin 10}^{(hIL-10) and another is by downregulation of the}^{Major Histocompatibility Complex}^{II (MHC II) in infected cells. The virus can be reactive by provocative stimuli can reactivate virus from the latent state, including axonal injury, fever, physical or emotional stress, and exposure to ultraviolet light. The virus follows axons back to the peripheral site, and replication proceeds at the skin or mucous membranes. Spontaneous reactivations occur in spite of HSV-specific humoral and cellular immunity in the host so that recurrent infections are less extensive and less severe. Many recurrences are asymptomatic, reflected only by viral shedding in secretions. When symptomatic, episodes of recurrent HSV-1 infection are usually manifested as cold sores (fever blisters) near the lip}

Herpes simplex Virus (HSV)
There are two distinct herpes simplex viruses: type 1 and type 2 (HSV-1, HSV-2) Their genomes are similar in organization and exhibit substantial sequence homology. However, they can be distinguished by sequence analysis or by restriction enzyme analysis of viral DNA. The two viruses cross-react serologically, but some unique proteins exist for each type.
Table 3. Comparison of Herpes Simplex Virus Type 1 and Type 2.}

^{CharacteristicsHSV-1HSV-2
Biochemical
  Viral DNA base composition (G + C)67%69%
  Buoyant density of DNA (g/cm3)
1.7261.728
  Buoyant density of virions (g/cm3)
1.2711.267
  Homology between viral DNAs~50%~50%
Biologic
  Animal vectors or reservoirsNoneNone
  Site of latencyTrigeminal gangliaSacral ganglia
Epidemiologic
  Age of primary infectionYoung childrenYoung adults
  TransmissionContact (often saliva)Sexual
Clinical
  Primary infection:
    Gingivostomatitis+-
    Pharyngotonsillitis+-
    Keratoconjunctivitis+-
    Neonatal infections±+
  Recurrent infection:
    Cold sores, fever blisters+-
    Keratitis+-
  Primary or recurrent infection:
    Cutaneous herpes
       Skin above the waist+±
       Skin below the waist±+
       Hands or arms++
    Herpetic whitlow++
    Eczema herpeticum+-
    Genital herpes±+
    Herpes encephalitis+-
    Herpes meningitis±+}

^{Diagnosis of HSV Infections
- Cytopathology
A rapid cytologic method is to stain scrapings obtained from the base of a vesicle (eg, with Giemsa s stain); the presence of multinucleated giant cells indicates that herpesvirus (HSV-1 or HSV-2) and contain Cow dry type A inclusion bodies Formation , In the course of viral multiplication within cells, virus-specific structures called inclusion bodies may be produced. They become far larger than the individual virus particle and often have an affinity for acid dyes (eg, eosin). They may be situated in the nucleus (herpesvirus), in the cytoplasm (poxvirus), or in both (measles virus). In many viral infections, the inclusion bodies are the site of development of the virions (the viral factories). Variations in the appearance of inclusion material depend largely upon the tissue fixative used. The presence of inclusion bodies may be of considerable diagnostic aid. The intracytoplasmic inclusion in nerve cells—the Negri body—is pathognomonic for rabies.

- Quantitation of Viruses
. The cells can also be stained with specific antibodies in an immunofluorescence test and it is also possible to detect viral DNA by in situ hybridization. Type-specific antibodies can distinguish between HSV-1 and HSV-2.
- Polymerase Chain Reaction (PCR)
PCR assays can be used to detect virus and are sensitive and specific. PCR amplification of viral DNA from cerebrospinal fluid has replaced viral isolation from brain tissue obtained by biopsy
- Serology
Antibodies appear in 4–7 days after infection and reach a peak in 2–4 weeks. They persist with minor fluctuations for the life of the host.
Treatment, Prevention, & Control
Several antiviral drugs have proved effective against HSV infections, including acyclovir, valacyclovir, and vidarabine. Acyclovir is currently the standard therapy. All are inhibitors of viral DNA synthesis. Acyclovir, a nucleoside analog, is monophosphorylated by the HSV thymidine kinase and is then converted to the triphosphate form by cellular kinases. The acyclovir triphosphate is efficiently incorporated into viral DNA by the HSV polymerase, where it then prevents chain elongation.
Vaccine
Recombinant HSV-2 glycoprotein ( that found in viral envelope ) can be used .} .

المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .