Post on 08-Jul-2015
description
PRESENTED BY
T. R . Divya, BMS10212,Final year M.Sc.,Department of Biomedical Science,School of Basic Medical Sciences,Bharathidasan University,Tiruchirappalli-620 024
UNDER THE GUIDANCE OFDr. K. SathiyamurthyAssistant Professor,Clinical Microbiology and Molecular Microbial
Pathogenesis Laboratory,Department of Biomedical Science,School of Basic Medical Sciences,Bharathidasan University,Tiruchirappalli-620 024
FINAL PRESENTATION 29-10-2014
HIV-1 PATHOGENESIS WITH SPECIAL REFERENCE TO
GENETIC FORMS
FIRST PRESENTATION
1. Introduction about HIV-1
2. Pathogenesis of HIV-1 in different cells
3. Genetic forms of HIV-1
4. My focus of Self-Study
INTRODUCTION
Human Immunodeficiency Virus type-1 (HIV-1) is a double singlestranded RNA virus. It belongs to the
Family : Retroviridae
Genus : Lentivirus
Species: Human Immunodeficiency Virus-1
(HIV-1)
It is an enveloped virus enters into the host cells by membranefusion mechanism (Goldsby et al., 2002).
It consists of nine important genes in its genomic structure. Themain gene involves in the pathogenicity and infectivity of theHIV-1 virus is env gene. It encodes precursor proteinglycoprotein 160 (gp 160) (David et al., 1998).
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EPIDEMIOLOGY OF HIV-1 According to the records of Joint United Nations Programme
on HIV and AIDS (UNAIDS) at 2011, 34 million people wasliving with HIV around the world. The same year 2.5 millionpeople are newly infected with HIV (Katherine et al., 2003).
1.Sub – Saharan Africa is the most affected area in the world.Here 67.6% of individuals living with HIV-1 infection and 72%of deaths because of AIDS.
2. In South Africa, 5.6 million HIV -1 infection and 17.2% oftotal AIDS mortality. In Asia there are 4.9 million infected withHIV - 1.
29-10-2014 Goldsby et al., 2004
Env GENE BINDING REACTION
Viral envelope protein (env) binds with targetcell in two ways. That are,
1. Specific interaction
2. Non – specific interaction
Specific interaction env + α4β7integrin or DC-SIGN
Non - Specific interaction env + heparansulfate proteoglycan
Craig et al., 201229-10-2014
GP 120 and GP 41 STRUCTUREGP 41:1.It involves in the final step of thefusion.2.It forms six - helix bundle (6HB)structure which leads to theformation of fusion pore.
GP 120:1.It is responsible for receptorbinding.2.It contains 5 relatively conserveddomains (C1-C5) and 5 variable loops(V1-V5).3.Each variable region forms loopstructure by disulfide bond(Himanshu et al., 2008).
David et al., 1998
Miklos et al., 201129-10-2014
SYNCYTIUM FORMATION
Felts et al., 201029-10-2014
Dendrictic cells
CD 4+ T cells
Matured HIV-1 virions in compartments
Filopodia
Fusion of HIV-1 virions into CD4+ T cells
GENETIC AND RECOMBINANT FORMS OF HIV-1
A AI, A2 and A3F F1 and F2
Michael et al., 2002, Joris et al., 2006 and Katherine et al., 2013
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Global distribution of HIV-1 subtypes and recombinants
in 2004. A; B; C ; D;
F,G,H,J,K CRF01_AE; CRF02_AG;
CRF03_AB ; other
Recombinants (Hemelaar et al., 2004)
A A1 and A2F F1 and F2
CONCLUSION
HIV-1 is a high heterogenicity in nature. Hence, it is very
challengeable among the investigators to design a vaccine or to
deliver a drug on target.
This review is may be useful for the HIV-1 interested groups
to understand the pathogenic mechanism of HIV-1 in different
cells and its genetic forms.
This will also provides significant information to find a new
drug targeting HIV-1 and vaccine preparation.
REFERENCES1. Craig B. Wilen, John C. Tilton and Robert W. Doms 2012 HIV: Cell
Binding and Entry. Cold Spring Harb Perspect Med.2. David C. Chan and Peter S. Kim 1998 HIV Entry and Its Inhibition. Cell,
Vol. 93, 681–684.3. Himanshu Garg and Robert Blumenthal 2008 Cell Mol Life Sci 65(20):
3134–3144.4. Jonathan Weber 2001 The pathogenesis of HIV-1 infection British
Medical Bulletin, 58: 61–72.5. Joris Hemelaar, Eleanor Gouws, Peter D. Ghys and Saladin Osmanov
2006 Global and regional distribution of HIV-1 genetic subtypes andrecombinants in 2004, AIDS, 20:W13–W23.
6. Stephen A. Gallo, Catherine M. Finnegan, Mathias Viard, Yossef Raviv,Antony Dimitrov, Satinder S. Rawat, Anu Puri, Stewart Durell, RobertBlumenthal 2003 The HIV Env-mediated fusion reaction Biochimica etBiophysica Acta, 1614, 36– 50.
7. Susan Moir, Tae-Wook Chun, and Anthony S. Fauci 2011 PathogenicMechanisms of HIV Disease Annu. Rev. Pathol. Mech. Dis., 6:223–48.
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REFERENCES
8. Yuntao Wu , Alyson Yoder 2009 Chemokine Coreceptor Signaling inHIV-1 Infection and Pathogenesis, PLoS Pathogens, Volume 5 , Issue12
9. Katherine A. Lau, Justin J.L. Wong 2013 Current trends of HIVrecombination worldwide, Infectious Disease Reports; volume5:s1e4,15-20.
10. Mario Stevenson 2003 HIV-1 Pathogenesis, Nature medicine,7: 853-860.
11. Michael M Thomson, Lucía Perez-Alvarez, and Rafael Najera 2002Molecular epidemiology of HIV-1 genetic forms and its significance forvaccine development and therapy, Lancet Infect Dis; 2: 461–71.
12. Roni Sarkar, Reshmi Pal, Baishali Bal, Ranajoy Mullick, SatarupaSengupta, Kamalesh Sarkar and Sekhar Chakrabarti 2011 GeneticCharacterization of HIV-1 Strains Among the Injecting Drug Users inNagaland, India. The Open Virology Journal,, 5, 96-102.
13. Sigall Kassutto and Eric S. Rosenberg 2004 Primary HIV type -1infection, Clinical infectious diseases;38;1447-1453
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