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Chapter 3 : Steps Involved in HIV:Cell Interaction and Virus Entry
Author:
Jay A. Levy1
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Affiliations:
1: Department of Medicine, Laboratory for Tumor and AIDS Virus Research and Cancer Research Institute University of California, School of Medicine San Francisco, California
Content Type: Monograph
Publication Year:
2007
Category: Viruses and Viral Pathogenesis
Book DOI:
10.1128/9781555815653
Chapter DOI:
10.1128/9781555815653.ch03
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Steps Involved in HIV:Cell Interaction and Virus Entry, Page 1 of 2
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Abstract:
Transmission of HIV requires the successful interaction of the virus with receptors on a cell surface. The sites on the virus and on the cells that are involved in this interaction, and the events required for viral entry, are reviewed in this chapter. The CD4 molecule may have a role in viral infection aside from its binding to the HIV envelope. Several early studies examining the role of the CD4:virus interaction in HIV infection indicated that the CD4 receptor alone was neither sufficient nor the sole means for viral entry. The identification of CXCR4 as an HIV coreceptor occurred shortly before other investigators began examining chemokine receptors in HIV infection. Certain cytokines can increase or decrease chemokine receptor expression, thus influencing virus infection and selection. Enveloped viruses, such as HIV, following attachment, enter cells after fusion with the cell membrane. Thus, three major steps can be involved in infection: attachment, fusion, and entry. The fusion process can be measured by membrane fluorescence dequenching. Investigators have shown that after attachment to CD4 a delay in viral entry at the cell surface can influence the spread of HIV and the extent of virus production. The chapter talks about down-modulation of the CD4 protein, infection of cells lacking CD4 expression, cell surface interactions, other possible mechanisms Involved in virus entry, and cell-to-cell transfer of HIV. The spread of HIV in the host results from production of infectious progeny and also by cell-to-cell transfer of virus and possibly by non-envelope-mediated processes.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
Figures
Steps Involved in HIV:Cell Interaction and Virus Entry
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig01
Figure 3.1
The gp120 binding sites on the CD4 molecule as determined by mutational analysis, displayed on this model of domain 1 (D1). The consensus is that Phe-43 and Arg-59 are likely contact sites for gp120, but there are various conclusions regarding Lys-35 and Lys-46. Reprinted from reference 3093 with permission.
10.1128/9781555815653/f0056-01_thmb.gif
10.1128/9781555815653/f0056-01.gif
Figure 3.1
The gp120 binding sites on the CD4 molecule as determined by mutational analysis, displayed on this model of domain 1 (D1). The consensus is that Phe-43 and Arg-59 are likely contact sites for gp120, but there are various conclusions regarding Lys-35 and Lys-46. Reprinted from reference 3093 with permission.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig02
Figure 3.2
Proposed processes involved in HIV infection of cells. (A) HIV approaches a cell. A region on the viral surface envelope protein, gp120, interacts with a domain on a cell surface receptor (e.g., CD4). (B) Top, The interaction causes a conformational change in gp120 (and perhaps CD4), potentially resulting in a proteolytic cleavage of gp120, most likely in the V3 loop. Bottom, This process results in an interaction of the external portion of gp41 (fusion domain) with a proposed fusion receptor (F) on the cell surface. (C) HIV fuses with the cell. Alternatively, the interaction of gp120 with CD4 could lead to removal of gp120, with subsequent exposure of gp41 to the cell surface (see Section II.A).
10.1128/9781555815653/f0058-01_thmb.gif
10.1128/9781555815653/f0058-01.gif
Figure 3.2
Proposed processes involved in HIV infection of cells. (A) HIV approaches a cell. A region on the viral surface envelope protein, gp120, interacts with a domain on a cell surface receptor (e.g., CD4). (B) Top, The interaction causes a conformational change in gp120 (and perhaps CD4), potentially resulting in a proteolytic cleavage of gp120, most likely in the V3 loop. Bottom, This process results in an interaction of the external portion of gp41 (fusion domain) with a proposed fusion receptor (F) on the cell surface. (C) HIV fuses with the cell. Alternatively, the interaction of gp120 with CD4 could lead to removal of gp120, with subsequent exposure of gp41 to the cell surface (see Section II.A).
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig03
Figure 3.3
Purified HIV-1SF2 was mixed with soluble CD4 and incubated for 1 to 8 h at 37°C. Subsequently, the viral envelope protein gp120 was extracted and examined by immunoblot procedures. Lanes 1 and 8, virus preparation without sCD4 incubated for 8 h; lane 2, virus preparation with 1 μg of sCD4 at time zero; lanes 3 to 7, virus and sCD4 mixed for 0.5, 1, 2, 4, and 8h, respectively. After incubation with sCD4, the cleavage of the envelope gp120 into 50- and 70-kDa proteins is evident, and this process continues over time. The site of cleavage appears to be in the V3 loop (4728).
10.1128/9781555815653/f0059-01_thmb.gif
10.1128/9781555815653/f0059-01.gif
Figure 3.3
Purified HIV-1SF2 was mixed with soluble CD4 and incubated for 1 to 8 h at 37°C. Subsequently, the viral envelope protein gp120 was extracted and examined by immunoblot procedures. Lanes 1 and 8, virus preparation without sCD4 incubated for 8 h; lane 2, virus preparation with 1 μg of sCD4 at time zero; lanes 3 to 7, virus and sCD4 mixed for 0.5, 1, 2, 4, and 8h, respectively. After incubation with sCD4, the cleavage of the envelope gp120 into 50- and 70-kDa proteins is evident, and this process continues over time. The site of cleavage appears to be in the V3 loop (4728).
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig04
Figure 3.4
HIV entry into cells. Three major steps involved in virus infection are depicted based on observations in cell culture (3589, 4251). Adapted from reference 2520 with permission.
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Figure 3.4
HIV entry into cells. Three major steps involved in virus infection are depicted based on observations in cell culture (3589, 4251). Adapted from reference 2520 with permission.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig05
Figure 3.5
Phenotypic mixing. When two viruses of two different types enter the same cell, the progeny produced will consist of the initial viruses and also viruses that have exchanged their outside coat. These new viruses then have the host range of the virus from which they derived their envelope. Reprinted from reference 2512, copyright 1977, with permission from Elsevier.
10.1128/9781555815653/f0073-01_thmb.gif
10.1128/9781555815653/f0073-01.gif
Figure 3.5
Phenotypic mixing. When two viruses of two different types enter the same cell, the progeny produced will consist of the initial viruses and also viruses that have exchanged their outside coat. These new viruses then have the host range of the virus from which they derived their envelope. Reprinted from reference 2512, copyright 1977, with permission from Elsevier.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig06
Figure 3.6
Coinfection of a human T-lymphocyte line with HIV-1 and the murine xenotropic retrovirus led to virus preparations that contained phenotypically mixed particles. Thus, the HIV genome enveloped in a xenotropic virus coat could infect a wide variety of animal cell lines previously resistant to HIV infection. (A) HUT 78 human T cells; (B) mink lung cells; (C) horse dermis cells; (D) goat esophagus cells (all magnifications, × 40). Reprinted from reference 596 with permission from Elsevier.
10.1128/9781555815653/f0074-01_thmb.gif
10.1128/9781555815653/f0074-01.gif
Figure 3.6
Coinfection of a human T-lymphocyte line with HIV-1 and the murine xenotropic retrovirus led to virus preparations that contained phenotypically mixed particles. Thus, the HIV genome enveloped in a xenotropic virus coat could infect a wide variety of animal cell lines previously resistant to HIV infection. (A) HUT 78 human T cells; (B) mink lung cells; (C) horse dermis cells; (D) goat esophagus cells (all magnifications, × 40). Reprinted from reference 596 with permission from Elsevier.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig07
Figure 3.7
Multinucleated cell formation in peripheral blood mono-nuclear cells infected by HIV-1. Magnification,×65.
10.1128/9781555815653/f0075-01_thmb.gif
10.1128/9781555815653/f0075-01.gif
Figure 3.7
Multinucleated cell formation in peripheral blood mono-nuclear cells infected by HIV-1. Magnification,×65.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03fig08
Figure 3.8
(A) Scanning electron micrograph of an HIV-infected, activated monocyte. The surface of most of the monocyte is characterized by irregular microvilli. However, the pseudopod of the monotype (top) is covered with small spherical structures which appear to be HIV virions. The bulges at the tips of these microvilli may be budding HIV virions. (From reference 3477 with permission.) (Figure continues next page) (B) Transmission electron micrograph of an activated monocyte showing a pseudo-pod with budding virus (top of figure). From reference 3477 with permission.
10.1128/9781555815653/f0075-02_thmb.gif
10.1128/9781555815653/f0075-02.gif
Figure 3.8
(A) Scanning electron micrograph of an HIV-infected, activated monocyte. The surface of most of the monocyte is characterized by irregular microvilli. However, the pseudopod of the monotype (top) is covered with small spherical structures which appear to be HIV virions. The bulges at the tips of these microvilli may be budding HIV virions. (From reference 3477 with permission.) (Figure continues next page) (B) Transmission electron micrograph of an activated monocyte showing a pseudo-pod with budding virus (top of figure). From reference 3477 with permission.
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
References
/content/book/10.1128/9781555815653.ch03
Tables
Steps Involved in HIV:Cell Interaction and Virus Entry
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab01
Table 3.1
Evidence suggesting another cellular receptor for HIV
Table 3.1
Evidence suggesting another cellular receptor for HIV
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab02
Table 3.2
Chemokine coreceptors of HIV infection
Table 3.2
Chemokine coreceptors of HIV infection
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab03
Table 3.3
List of some of the chemokines associated with the hematopoietic system
a
Table 3.3
List of some of the chemokines associated with the hematopoietic system a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab04
Table 3.4
Characteristics of R5 and X4 isolates of HIV
a
Table 3.4
Characteristics of R5 and X4 isolates of HIV a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab05
Table 3.5
Genotype frequencies of CCR5
a
Table 3.5
Genotype frequencies of CCR5 a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab06
Table 3.6
Effect of cytokines on CCR5 and CXCR4 chemokine receptor expression
a
Table 3.6
Effect of cytokines on CCR5 and CXCR4 chemokine receptor expression a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab07
Table 3.7
Factors involved in modulation of CD4 protein expression
Table 3.7
Factors involved in modulation of CD4 protein expression
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab08
Table 3.8
CD4–human cells susceptible to HIV infection
a
Table 3.8
CD4–human cells susceptible to HIV infection a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab09
Table 3.9
HIV:cell surface binding interactions
Table 3.9
HIV:cell surface binding interactions
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab10
Table 3.10
Other possible cellular binding proteins for HIV
Table 3.10
Other possible cellular binding proteins for HIV
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03
/content/10.1128/9781555815653.ch03.ch03tab11
Table 3.11
Steps involved in HIV infection of a cell
a
Table 3.11
Steps involved in HIV infection of a cell a
Citation:
Levy J.
2007.
Steps Involved in HIV:Cell Interaction and Virus Entry,
p 55-78.
In
HIV and the Pathogenesis of AIDS, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815653.ch03