Research on human herpes viruses: Worldwide and in...

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“Вирүс судлалын тулгамдсан асуудлууд”, Үндэсний 14 дүгээр бага хурал, 2013.09.27

Research on human herpes viruses:Worldwide and in Mongolia

Prof.P.Nymadawa, MD, PhD, DSc(Med)

Mongolian Society of Virology,

Mongolian Academy of Medical Sciences


Академич П.Нямдаваа 2

1. About herpes viruses

2. History (till 2000)

3. Current stand (2000-2013)

4. Future (2014 and further)

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About herpes viruses I: Structure

100 нм

Electron microscopic imagewof a herpes virus (negative

contrast staining, magnification: х100 000)

Herpes virus schematic drawing

Genome map of a herpes virus

Herpes viruses are wide spread in the nature, in animal, bird, amphibia and human populations. At the current stage there are over 200 viruses discovered from different hosts, including 9 genera found in human population.



About herpesviruses II: Taxonomic classification

БагОвог төрөлтөрөлтөрөлтөрөл

ОвогДэд овогтөрөлтөрөлтөрөлтөрөл

Дэд овогтөрөлтөрөлтөрөлтөрөл

Дэд овогтөрөлтөрөлтөрөлтөрөл

Овогтөрөл

species genera subfamilies

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-400 300 1000 1500 1800 1940 1990 2000


Corner stones in the history of study of herpes virus infections

Worldwide

In MongoliaХомхой долоох

Домын судрууд

1955: varicella was included in the list of infectious dieases for obligatory registration

410-400 BC: herpesέρπής from, έρπέίν (herpein)Greek werb meaning: to creep

Hippocrates (460-377 BC)

≈100: herpes labialisHerodotos (?)

1736: herpes genitalisJean Astruc(1684-1766)

1767: varicellaWilliam Heberden

(1710-1801)

1913: experimental transmission of infection on rabbit cornea by herpes vesicle liquid

Wilhelm Grűter (1882-1963)

1953-1958: isolation and cultivation of HHV and VZV in cell culture

Thomas Huckle Weller (1915-2008)

1888: varicella and zoster

Janus von Bokay

1690: Амны хижиг өвчин,Бэлгэсийн завсар нэвчих өвчин,Могой үлд, Цагаан эсэргэнэ

Дэсрид Санжаажамц“Манаг лхантав”

≈1950: герпес (уруулын ба бэлгийн), ам гэмтэх, бүслэх үлд (могой яр),салхин цэцэг

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Clinical manifestations of HHV 1&2



Varicella and zoster (HHV 3)


Varicella rash

Zoster

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Corner stones in the history herpes virus study: 1950-2000

1953-1958: HHV-1/2, VZVT.H.Weller et al.

Worldwide

In Mongolia1985: trial of experimental treatment of keratisits with iod-deoxi-uridine

Э.Санжаа, П.Нямдаваа, Ш.Тумбааш Ж.Баасанхүү

1964: EBV (HHV-4)M.A.Epstein, Y.Barr

1957: CMV (HHV-5)T.H.Weller et al.

1986: HHV-6R.Gallo et al.

1974: Live varicella vaccine (Oka)

M.Takahashi et al.

1977-1982: acyclovir (zovirax)G.B.Elion нар, SKB

1990: HHV-7N.Frenkel et al.

1994: HHV-8Y.Chang et al.

1971: genus HerpesvirusICTV

1976: family HerpetoviridaeICMV

1993-1998: Fomivirsen (vitavene)

Isis Pharmaceuticals

1988: HHV-1 whole genome sequenceD.J.McGeach et al.


Burkitt’s lymphome and infectious mononucleosisHHV 4)


An african child with Burlitt’s lymphoma -an aggressive B lymphocyte sarcoma. Discovered in 1958 by Dr Denis Parsons Burkitt (1911-1993).

EBV was discovered in 1964 by UK electron microscopists Dr Michael Antony Epstein (b.1921), and Ms Yvonne Barr (b.1932) in the tissues from Burkitt’s lymphoma.

US virologists DrsGertrude Henle, Werner Henle have revealed in 1986 antibodies against EBV in sera of patients recovered from infectious mononucleosis.

Infectious mononucleosis is an infectious disease of children with fever and enlargement of lymph nodes accompanied by an appearance of atypical cells resembling monocytes in the blood smear. First described in 1885 by a famous russianpediatrician Нил Фёдорович Филатов (1847-1902).

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Cytomagaly (CMV: HHV-5)


Blood smear of a patient with cytomegaly


Exanthema subitum: (HHV-6A/6B, HHV7)


Exanthema subitum patient

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Капоши сарком (HHV-8)


HHV-8 was discovered first in 1994 from the tissue probes of a patient with Kaposi sarcoma.

However, this malignant change of skin was described first in 1872 by Moritz Kaposi (1837-1902), dermatolodyprofessor of Vienna, and it coined the name: Idiopathisches multiples Pigmentsarkom der Haut (idiopathic multiple pigmented sarcoma of skin).


Antivirals against herpes viruses


Acyclovir – a guanosine analogue Formiversen: compositanti-sense RNA

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Registered varicella cases in Mongolia (1952-2000)



Registered varicella cases in Mongolia in age-groupes (by average of 1998-2000)


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Stury on herpes viruses: 2000-2013 он

Worldwide

In Mongolia2002: Laboratory diagnosis and treatment of HHV-1/1 infections(PhD)

П.Эрдэнэчимэг

2012: Genotypes of HHV-3 detected in Mongolia (PhD)

Д.Энхсайхан

2000-2010: famciclovir, ganciclovir, penciclovir, valaciclovir, valganciclovir

Molecular biology of herpes viruses

2009: order HerpesviralesICTV

2010: HHV-3 mongolian strains11 sequences of tegument protein

D.Enkhsaikhan et al.

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Registered varicella cases in Mongolia (1952-2012)



Monthly dynamics of the registered varicella cases in Mongolia (by the average of 2002-2008)


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Phylogenetic tree of VZV detected in Mongolia


D.Enkhsaikhan et al., 2012







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Challenges in Mongolia

• Expected increase of varicella cases: consideration of effective control measures including vaccination.

• Expected increase of zoster: consideration to include obligatory registration and vaccination.

• Consideration to introduce laboratory diagnosis of HHV-4, HHV-5, HHV-6, HHV-7 for non-measles, non-rubella fever/rash diseases,

• Consideration of introduction of anti-herpes antivirals for management of herpes virus encephalitis, Kaposi sarcoma and other complicated herpes virus infections under laboratory control of virus burden.


Trends of varicella cases in Mongolia


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ACKNOWLEDGEMENTS

The author thanks:

- Prof.Sh.Bold, MD, PhD, DSc(Med), member of MAS and MAMS for his valuable advises on

history of herpes infections in Mongolia

in ancient times,

- Mr B.Gantsooj for his support in preparation

of the slides.


Thank you for your attention

Research on human herpes viruses: Worldwide and in...

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