This document summarizes HIV-1 pathogenesis with a focus on genetic forms. It discusses how HIV-1 enters cells through envelope protein binding and membrane fusion. The virus infects CD4+ T cells and dendritic cells, forming syncytia. It describes the structure and roles of the envelope glycoproteins GP120 and GP41 in fusion. The document also outlines the major genetic subtypes and recombinants of HIV-1 globally. It concludes that HIV-1's high genetic variability poses challenges for vaccine and drug development.

1. HIV-1 PATHOGENESIS WITH
SPECIAL REFERENCE TO
GENETIC FORMS
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 OF
Dr. K. Sathiyamurthy
Assistant 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

2. 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

3. INTRODUCTION
 Human Immunodeficiency Virus type-1 (HIV-1) is a double single
stranded 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 membrane
fusion mechanism (Goldsby et al., 2002).
 It consists of nine important genes in its genomic structure. The
main gene involves in the pathogenicity and infectivity of the
HIV-1 virus is env gene. It encodes precursor protein
glycoprotein 160 (gp 160) (David et al., 1998).
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4. EPIDEMIOLOGY OF HIV-1
 According to the records of Joint United Nations Programme
on HIV and AIDS (UNAIDS) at 2011, 34 million people was
living with HIV around the world. The same year 2.5 million
people 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% of
total AIDS mortality. In Asia there are 4.9 million infected with
HIV - 1.
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5. HIV-1 PATHOGENESIS
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6. Env GENE BINDING REACTION
Viral envelope protein (env) binds with target
cell in two ways. That are,
1. Specific interaction
2. Non – specific interaction
 Specific interaction env + α4β7
integrin or DC-SIGN
 Non - Specific interaction env + heparan
sulfate proteoglycan
Craig et al., 2012
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7. GP 120 and GP 41 STRUCTURE
GP 41:
1.It involves in the final step of the
fusion.
2.It forms six - helix bundle (6HB)
structure which leads to the
formation of fusion pore.
GP 120:
1.It is responsible for receptor
binding.
2.It contains 5 relatively conserved
domains (C1-C5) and 5 variable loops
(V1-V5).
3.Each variable region forms loop
structure by disulfide bond
(Himanshu et al., 2008).
David et al., 1998
29-10-2014 Miklos et al., 2011

8. FUSION MECHANISM
Stephen et al., 2003
Wilen et al., 2012
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9. SYNCYTIUM FORMATION
Dendrictic cells
CD 4+ T cells
Matured HIV-1 virions in
compartments
Filopodia
Fusion
of HIV-1
virions
into
CD4+ T
cells
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10. COMPARISON OF SIGNALING PATHWAY
29-10-2014 Yuanto et al., 2009

11. GENETIC AND RECOMBINANT FORMS
OF HIV-1
Michael et al., 2002, Joris et al., 2006 and
Katherine et al., 2013
A AI, A2 and A3
F F1 and F2
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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 A2
F F1 and F2

12. 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.

13. REFERENCES
1. 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 and
recombinants 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, Robert
Blumenthal 2003 The HIV Env-mediated fusion reaction Biochimica et
Biophysica Acta, 1614, 36– 50.
7. Susan Moir, Tae-Wook Chun, and Anthony S. Fauci 2011 Pathogenic
Mechanisms of HIV Disease Annu. Rev. Pathol. Mech. Dis., 6:223–48.
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14. REFERENCES
8. Yuntao Wu , Alyson Yoder 2009 Chemokine Coreceptor Signaling in
HIV-1 Infection and Pathogenesis, PLoS Pathogens, Volume 5 , Issue
12
9. Katherine A. Lau, Justin J.L. Wong 2013 Current trends of HIV
recombination worldwide, Infectious Disease Reports; volume
5: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 2002
Molecular epidemiology of HIV-1 genetic forms and its significance for
vaccine development and therapy, Lancet Infect Dis; 2: 461–71.
12. Roni Sarkar, Reshmi Pal, Baishali Bal, Ranajoy Mullick, Satarupa
Sengupta, Kamalesh Sarkar and Sekhar Chakrabarti 2011 Genetic
Characterization of HIV-1 Strains Among the Injecting Drug Users in
Nagaland, India. The Open Virology Journal,, 5, 96-102.
13. Sigall Kassutto and Eric S. Rosenberg 2004 Primary HIV type -1
infection, Clinical infectious diseases;38;1447-1453
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15. THANK YOU
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