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Journal of Virology, December 2000, p. 11955-11962, Vol. 74, No. 24
Aaron Diamond AIDS Research Center, The
Rockefeller University, New York, New York
10016,1 and Department of Cancer
Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical
School,2 and Department of Immunology
and Infectious Diseases, Harvard School of Public
Health,3 Boston, Massachusetts 02115
Received 28 April 2000/Accepted 12 September 2000
The in vivo passage of a neutralization-sensitive,
laboratory-adapted simian-human immunodeficiency virus (SHIV-HXBc2)
generated a pathogenic, neutralization-resistant virus, SHIV-HXBc2P
3.2. SHIV-HXBc2P 3.2 differs from SHIV-HXBc2 only in 13 amino acid residues of the viral envelope glycoproteins. Here we used antibody competition analysis to examine the structural changes that occurred in
the SHIV-HXBc2P 3.2 gp120 exterior envelope glycoprotein. The relationships among the antibody epitopes on the conserved gp120 core
of SHIV-HXBc2 and SHIV-HXBc2P 3.2 were similar. The third variable (V3)
loop was more closely associated with the fourth conserved (C4) region
and CD4-induced epitopes on the gp120 core in the HXBc2P 3.2 gp120
glycoprotein compared with the HXBc2 gp120 glycoprotein. Rearrangements
of the second variable (V2) loop with respect to the CD4 binding site
and associated epitopes were evident in comparisons of the two gp120
glycoproteins. Thus, the in vivo evolution of a
neutralization-resistant virus involves conformational adjustments of
the V2 and V3 variable loops with respect to the conserved
receptor-binding regions of the gp120 core.
Human immunodeficiency virus type 1 (HIV-1) has evolved mechanisms to evade the humoral immune response to
its envelope glycoproteins, gp120 and gp41 (20). This is a
property that HIV-1 shares with other lentiviruses (1, 5, 14, 15,
20), suggesting that it might be necessary for the development or
maintenance of a persistent, transmissible infection in vivo. The
evasion mechanism(s) is manifested by the restricted ability of
potentially neutralizing antibodies to bind to the native, trimeric
form of the fusogenic envelope glycoprotein complex, as it exists on
the surface of virions or virus-infected cells (20). In most
well-studied examples, antibody binding to this complex results in
virus neutralization. In most cases, neutralization occurs by
inhibition of the binding of virions to the CD4 antigen and the
coreceptor molecules, associations that trigger conformational changes
in the viral envelope glycoproteins and hence virus-cell fusion
(20, 27, 28, 29).
Upon in vitro passage of HIV-1, structural changes occur in the
envelope glycoproteins that are associated with the acquisition of a
more neutralization-sensitive phenotype, perhaps as an indirect consequence of selection for viral variants that more efficiently interact with cell surface receptors (20). How this occurs
is not yet well understood. However, studying the antibody response to
the HIV-1 envelope glycoproteins during natural infections has been
facilitated by the development of the simian-human immunodeficiency virus (SHIV)-monkey model (12, 13, 21, 23). SHIVs are recombinant viruses in which segments of the HIV-1 genome (typically the tat, rev, vpu, and env
genes) are inserted into a simian immunodeficiency virus backbone.
SHIVs therefore express HIV-1 envelope glycoproteins yet, unlike HIV-1,
efficiently infect monkeys (12, 13, 21, 23). One of the
prototypic SHIVs was SHIV-HXBc2, which contains the envelope
glycoproteins derived from a T-cell line-adapted X4 HIV-1 strain
(12). SHIV-HXBc2, like HIV-1 HXBc2, is sensitive to most of
the neutralizing monoclonal antibodies (MAbs) that are able to
recognize epitopes present on the HXBc2 envelope glycoproteins (10, 11). In rhesus macaques, SHIV-HXBc2 replicated only to low levels and did not cause pathology within a 3-year period (11). Repeated in vivo passage of SHIV-HXBc2 resulted in the generation of a virus called KU-1 that could cause rapid
CD4+ T-lymphocyte depletion and AIDS in infected monkeys
(8). The KU-1 env gene was cloned and inserted
into the parental SHIV-HXBc2 to create SHIV-HXBc2P 3.2, a virus that
caused precipitous CD4+ T-lymphocyte loss and induced
AIDS-like disease in rhesus macaques (4). Thus, mutations
within the KU-1 env gene that resulted in only a few amino
acid differences from the HXBc2 envelope glycoproteins were sufficient
to account for the acquired immunopathogenicity of SHIV-HXBc2P 3.2. SHIV-HXBc2P 3.2 was also significantly more resistant to neutralization
by soluble CD4 and neutralizing antibodies than the parental SHIV-HXBc2
(4). However, the epitopes for the neutralizing MAbs were
retained on the monomeric SHIV-HXBc2P 3.2 gp120 envelope glycoprotein
(4). Thus, in vivo passage of a virus expressing
neutralization-sensitive HIV-1 envelope glycoproteins generated a
closely related virus with a high degree of neutralization resistance,
a property typical of primary HIV-1 isolates.
The envelope glycoprotein changes that occurred in the SHIV-HXBc2P 3.2 envelope glycoproteins upon in vivo passage are shown in Fig.
1. Compared with the parental HXBc2
envelope glycoproteins, the HXBc2P 3.2 envelope glycoproteins exhibit
changes in five regions: the first variable/second variable (V1/V2)
stem-loops, the second conserved (C2) region, the V3 region, the V5
region, and the gp41 ectodomain. The locations and nature of these
changes are of interest. Three of the changes occur within the V1/V2
stem-loop structure, which has been implicated in modulation of
neutralization sensitivity in other contexts (3, 32, 33).
One of the observed changes, within the V1 loop, involves the
acquisition of an N-linked glycosylation site in the HXBc2P 3.2 envelope glycoprotein. Sugar moieties hypothetically could contribute
to steric masking of neutralization epitopes on the HIV-1 envelope
glycoproteins. Conversely, loss of N-linked glycosylation sites at
particular locations could assist in the tighter packing of envelope
glycoprotein regions involved in the masking of neutralization
epitopes. Three of the HXBc2P 3.2-associated changes, one in the C2
region and two in the gp41 ectodomain, involve the loss of potential
N-linked glycosylation sites. The C2 change occurs in the gp120
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Association of Structural Changes in the V2 and V3
Loops of the gp120 Envelope Glycoprotein with Acquisition of
Neutralization Resistance in a Simian-Human Immunodeficiency Virus
Passaged In Vivo
and
ABSTRACT
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loop, which is located within a heavily glycosylated, outer domain rim
that flanks the recessed CD4-binding region of gp120 (9,
31). Four amino acid changes occur in the base of the V3 loop,
another region that can modulate HIV-1 neutralization sensitivity
(7, 25, 34). None of these changes involve V3 residues
previously implicated in coreceptor interactions (24),
consistent with our observations that both HXBc2 and HXBc2P 3.2 envelope glycoproteins utilize the CXCR4 receptor almost exclusively
(4). Finally, two residues within the HXBc2P 3.2 gp120 V5
region are altered compared with the gp120 glycoprotein of the parental
HXBc2 virus.
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FIG. 1.
Comparison of primary amino acid sequences of the HXBc2
and HXBc2P 3.2 envelope glycoproteins. The HIV-1 gp120 glycoprotein and
part of the gp41 glycoprotein are depicted. S, signal peptide; TM,
transmembrane region; V1 to V5, gp120 variable regions; C1 to C5, gp120
conserved regions. The arrow denotes the gp120-gp41 cleavage site.
Residues that differ between the HXBc2 and HXBc2P 3.2 envelope
glycoproteins are denoted by numbers, with the amino acid in
single-letter code noted beneath the sequence.
To examine the structural basis of neutralizing antibody resistance, we performed a comparative topological analysis of the antibody epitopes on the monomeric forms of the HXBc2 and HXBc2P 3.2 gp120 exterior envelope glycoproteins, using procedures described in detail elsewhere (2, 18). The sources of monomeric gp120s from HXBc2 and HXBc2P 3.2 were culture supernatants from 293T cells transfected with the respective env genes. The gp120 proteins were captured directly from the supernatants onto a solid phase by adsorbed sheep polyclonal antibody D7324 (2, 18, 19). This antibody was raised to a peptide spanning the C-terminal 15 amino acids of HIV-1 LAI, a well-conserved region that is proximal to a segment of the gp41-binding site on gp120 (6, 16, 30). Via D7324, the gp120 molecule is captured with a geometry that roughly mimics its orientation on virions, with the position of the solid phase corresponding to that of the viral membrane. Antibodies are able to react with exposed epitopes on the captured gp120 proteins (18).
In initial experiments, antibody titration curves were performed with
biotin-labeled MAbs (bio-MAbs) to determine the relative affinities of
each MAb for the HXBc2 and HXBc2P 3.2 gp120 glycoproteins. The
concentration of each bio-MAb required to achieve 50% of maximal binding to the two gp120 glycoproteins is shown in Table
1. All antibodies used in the study
exhibited roughly similar affinities for the HXBc2 and HXBc2P 3.2 gp120
glycoproteins, with the exception of two V3 loop-directed antibodies.
The G3-1472 and 110.I antibodies both bound the HXBc2P 3.2 gp120
glycoprotein with lower affinity than the HXBc2 envelope glycoprotein.
This difference in affinity probably results from a subset of the V3
loop sequence differences between HXBc2 and HXBc2P 3.2 gp120
glycoproteins. The binding curves of the bio-MAbs were used to select
the optimal concentration of each bio-MAb to use in the
cross-competition experiments. Typically, we used a bio-MAb
concentration that led to the generation of a signal at an optical
density at 492 nm of approximately 1.20, which usually represented
approximately 70% of the saturating binding concentration.
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The antibody cross-competition analysis was performed by measuring the extent of the binding of each bio-MAb, at its predetermined, optimal concentration, to gp120 in the presence or absence of competitor MAbs. The competitors were added at a fixed concentration of 5 or 10 µg/ml, this usually representing a saturating concentration. Each competitor MAb was tested in triplicate, and each experiment was usually performed three or more times, ensuring that at least nine individual enzyme-linked immunosorbent assay wells contribute to the datum point for each competitor MAb. The extent of bio-MAb binding in the absence of the competitor MAb was defined as 100%. The ratio between the binding of the bio-MAb in the presence and absence of each competitor was then calculated as a percentage. A value of <50% is indicative of significant inhibition of the binding of the bio-MAb by the competitor; one of >125% means that the competitor MAb has enhanced the binding of the bio-MAb, most probably by inducing a conformational change in the gp120 molecules that improves the accessibility or integrity of the epitope for the bio-MAb (2, 18).
The antibody competition matrices are shown in Fig.
2. We have
highlighted in color on the matrices those MAb combinations that lead
to significant and highly reproducible differences in the extent of
competition observed when the HXBc2 and HXBc2 3.2P gp120s are compared.
Competition values that differ by 
40% between the HXBc2 and HXBc2P
3.2 gp120 glycoproteins are thus colored according to the observed
degree of inhibition or enhancement.
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Figure 3 shows a difference map, which
highlights competition values that exhibit 40% difference between
the two gp120 glycoproteins. Green squares indicate instances where
either a more positive or more negative effect of competitor MAb
binding was observed for the HXBc2P 3.2 gp120 than for the HXBc2 gp120.
In those instances where differences in MAb affinity for the two
glycoproteins do not explain the results, the more pronounced effects
of competitor MAb binding indicate a closer relationship of the two
epitopes on the HXBc2P 3.2 gp120 glycoprotein. A less positive or
negative effect of competitor MAb binding for the HXBc2P 3.2 gp120 than for the HXBc2 gp120 probably indicates a more distant relationship between the antibody epitopes on the HXBc2P 3.2 gp120 glycoprotein, in
those instances where the results cannot be explained by differences in
MAb affinity for the HXBc2 and HXBc2P 3.2 gp120 glycoproteins.
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Several general features of the difference map are noteworthy. There are 35 green squares but only 13 red and 12 yellow squares. The predominance of green squares suggests that there may be a greater overall proximity of antibody epitopes on the HXBc2P 3.2 gp120 glycoprotein than on the HXBc2 gp120 glycoprotein. The general positions of the highlighted squares on the matrix are also revealing. The paucity of highlighted squares in the upper left quadrant, which details the relationship between conserved epitopes in the gp120 core, indicates little overall difference between the antigenic structures of the HXBc2 and HXBc2P 3.2 gp120 cores. This is consistent with the locations of most of the amino acid differences between the two proteins in the gp120 variable regions (Fig. 1). It is also consistent with the expectation that the intra- and interdomain relationships in the gp120 core will be conserved among virus variants. This expectation is based on the high degree of conservation of the gp120 residues within the core domains and in the domain interfaces in primate immunodeficiency viruses (9, 31).
The upper right quadrant of the difference map is heavily populated with highlighted squares, indicating substantial differences between HXBc2 and HXBc2P 3.2 gp120 glycoproteins in the relationship of the major variable loops, V2 and V3, to the conserved core (Fig. 3). That most of these squares are green suggests that the V2 and V3 loops interact more intimately with the HXBc2P 3.2 gp120 core than with the HXBc2 core. It is noteworthy that the lower left quadrant, which details the reciprocal effects of variable loop-directed MAbs on the binding of MAbs against the gp120 core, is less populated than the upper right quadrant. This indicates that MAb binding to a gp120 core epitope is more likely to register an effect on the binding of a variable loop-directed MAb than vice versa. Some insight into this observation derives from recent studies indicating an unusually high degree of flexibility among the gp120 core domains (19a). Ligands that bind the conserved, discontinuous structures in the gp120 core decrease this flexibility and limit the accessibility of gp120 to other ligands quite effectively (P. Kwong, R. Wyatt, W. Hendrickson, and J. Sodroski, unpublished observations). In contrast, MAbs against the gp120 variable loops do not alter the flexibility of the core; thus, the subsequent binding of ligands to the core involves a relatively flexible structure, diminishing the steric impact of the already bound antibody.
Specific highlighted data points within the difference map arise from two sources: (i) differences in the relative affinities of MAbs for the HXBc2 and HXBc2P 3.2 gp120 glycoproteins and (ii) conformational changes between the two gp120 molecules that alter the relationship of epitopes on the gp120 surface. The observed differences between the gp120 glycoproteins in the competition of the G3-1472 V3 MAb by several MAbs probably arises from the significantly lower affinity of the G3-1472 MAb for the HXBc2P 3.2 glycoprotein. Likewise, the differences observed for the HXBc2 and HXBc2P 3.2 glycoproteins in the ability of the 17b and 48d antibodies to compete for binding of the 110.I and possibly the 110.J anti-V3 MAbs could be a consequence of the somewhat lower affinity of these V3 MAbs for the HXBc2P 3.2 gp120. The altered pattern of V3 MAbs competing for the binding of other V3 MAbs to the two gp120 glycoproteins reflects the relative affinities of these MAbs for the HXBc2P 3.2 gp120 glycoprotein.
Most of the observed differences in the competition maps between the HXBc2 and HXBc2P 3.2 gp120 glycoproteins cannot, however, be explained by variation in the relative affinities of the involved MAbs for the two gp120 glycoproteins. The effects of C4-directed MAbs on the 110.I and 110.J V3 MAbs, as well as on the 110.5 MAb, likely reflect a decreased distance between the C4 and V3 regions on the HXBc2P 3.2 gp120 glycoprotein. The 48d antibody against a CD4-induced (CD4i) epitope also exhibits a greater effect on the binding of the 110.5 V3 MAb to the HXBc2P 3.2 gp120 glycoprotein. This is consistent with a V3 loop position on the HXBc2P 3.2 gp120 glycoprotein that is closer to the CD4i and C4 epitopes, which overlap considerably (9, 26, 31). The increased proximity of the V3 loop to the C4 and CD4i epitopes also explains the effects of G3-519 and 17b, C4 and CD4i MAbs, respectively, on the binding of the 48d antibody. The latter antibody recognizes a CD4i epitope but is strongly influenced by the V3 loop conformation and may even recognize elements of V3 as part of its epitope (26, 33). Thus, the few altered relationships among core epitopes of the HXBc2P 3.2 gp120 that are evident in the difference map involve core structures exhibiting intimate relationships with a variable loop.
The conformation of the V2 variable loop must also change in the HXBc2P 3.2 gp120 glycoprotein relative to that in the HXBc2 glycoprotein. The behavior of the V2 MAbs indicates the existence of two subsets of these epitopes. Most V2 epitopes appear to be closer to the CD4-binding site (CD4BS) and C4 epitopes in the HXBc2P 3.2 gp120 glycoprotein. By contrast, the SC258 epitope appears to be more distant from many gp120 epitopes in the HXBc2P 3.2 gp120 glycoprotein. Although this potentially could result from a lower affinity of the SC258 MAb for the HXBc2P 3.2 gp120 glycoprotein than for the HXBc2 gp120, direct assessment of the SC258 binding affinities for the two gp120 glycoproteins did not reveal any significant difference (Table 1). Together these data suggest conformational rearrangements within the V2 loop as well as movement of the V2 loop in relationship to the HXBc2P 3.2 gp120 core.
The 2G12 epitope, which is a carbohydrate-dependent structure (26a), does not appear to change its relationship to other gp120 epitopes in the HXBc2P 3.2 glycoprotein compared with the HXBc2 glycoprotein. This is consistent with the location of the 2G12 epitope on the gp120 outer domain (31). The 2G12 epitope is thus removed from the other gp120 neutralization epitopes, including the variable loops (18).
The antibody competition analysis was used to create models of the
HXBc2 and HXBc2P 3.2 gp120 monomers (Fig.
4). In the models, the gp120 core
corresponds to the HXBc2 structure crystallized in a complex with
soluble CD4 and the Fab fragment of a CD4i antibody (9, 31).
As discussed above, it is likely that free gp120 can assume many
conformations (19a). However, as the only available detailed
structure of the HIV-1 gp120 core is derived from this ternary complex,
we have chosen to use it here. The assumptions underlying the models
are that once the effects attributable to MAb affinity differences are
eliminated, greater positive or negative effects in the antibody
competition analysis indicate increased epitope proximity; thus, green
squares in the difference map are modeled as greater proximity between
the epitopes on the HXBc2P 3.2 gp120 glycoprotein compared with those
on the HXBc2 gp120 glycoprotein. Additional constraints on the origins
of the V2 and V3 strands imposed by the gp120 core structure
(9) have been considered in the models.
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5 Å away (center-to-center distance) from CD4 and 17b in
the ternary complex crystal (Comparison of the models reveals a movement of the V2 and V3 loops in the HXBc2P 3.2 gp120 glycoprotein relative to the positions assumed in the HXBc2 gp120. A consequence of this movement is the approximation of the variable loops and the conserved neutralization epitopes near the receptor-binding regions. In particular, the conserved gp120 region near the CD4i epitopes that is implicated in chemokine receptor binding (22) is more effectively masked in the HXBc2P 3.2 gp120 model. This would essentially sequester the HXBc2P 3.2 chemokine receptor-binding surface from potentially neutralizing antibodies until binding to host cell CD4 occurs, at which time steric constraints limit the interaction of these antibodies with their epitope on gp120 (25). Masking of the receptor-binding regions of the HXBc2P 3.2 gp120 glycoprotein was not observed simply by measuring the affinity of MAbs directed against the CD4BS, CD4i, or C4 epitopes for the monomeric gp120 glycoproteins (Table 1). Such masking may be subtle in this context or difficult to detect due to the conformational flexibility of free gp120, alluded to above. Presumably, on the functional HIV-1 envelope glycoprotein trimer, the more limited flexibility results in an improved effectiveness of the overlying variable loops in diminishing recognition of the conserved epitopes by neutralizing antibodies.
The results are consistent with predictions made regarding the structural differences between primary and laboratory-adapted HIV-1 envelope glycoproteins (17a) and with the genetic mapping of neutralization resistance determinants within the gp120 glycoproteins of other primary HIV-1 isolates (5a, 25). Additional studies mapping the genetic determinants of neutralization resistance of SHIV-HXBc2P 3.2 should provide additional details of the structural basis of this resistance. It will be particularly important to understand the structural differences between the HXBc2 and HXBc2P 3.2 envelope glycoproteins in the context of the virion-associated oligomer. This understanding can guide attempts at intervention against HIV-1 infection by drugs and vaccines.
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ACKNOWLEDGMENTS |
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We thank the suppliers of MAbs and soluble CD4.
This work was supported by grants AI 39420, AI 36082, and AI 31783 from the National Institutes of Health. This work was also supported by the G. Harold and Leila Y. Mathers Foundation, the late William F. McCarty-Cooper, the Friends 10, and Douglas and Judith Krupp. J.P.M. is an Elizabeth Glaser Scientist of the Pediatric AIDS Foundation.
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FOOTNOTES |
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* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney St., JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu.
Present address: Department of Microbiology and Immunology, Joan
and Sanford I. Weill Medical College of Cornell University, New York,
NY 10021.
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REFERENCES |
|---|
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Abstract
Text
References
|
|---|
| 1. |
Baldinotti, F.,
D. Matteucci,
P. Mazzetti,
C. Gianelli,
P. Bandecchi,
F. Tozzini, and M. Bendinelli.
1994.
Serum neutralization of feline immunodeficiency virus is markedly dependent on passage history of the virus and host system.
J. Virol.
68:4572-4579 |
| 2. | Binley, J., R. Wyatt, E. Desjardins, P. Kwong, W. Hendrickson, J. Moore, and J. Sodroski. 1997. Analysis of the interaction of antibodies with a conserved, enzymatically deglycosylated core of the HIV-1 gp120 envelope glycoprotein. AIDS Res. Hum. Retroviruses 14:191-198. |
| 3. | Cao, J., N. Sullivan, E. Desjardins, C. Parolin, J. Robinson, R. Wyatt, and J. Sodroski. 1997. Replication and neutralization of human immunodeficiency virus type 1 lacking the V1/V2 variable loops of the gp120 envelope glycoprotein. J. Virol. 71:9808-9812[Abstract]. |
| 4. |
Cayabyab, M.,
G. Karlsson,
B. Etemad-Moghadam,
W. Hofmann,
T. Steenbeke,
M. Halloran,
J. Fanton,
M. Axthelm,
N. Letvin, and J. Sodroski.
1999.
Changes in the HIV-1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2).
J. Virol.
73:976-984 |
| 5. | Cook, R. F., S. L. Berger, K. E. Rushlow, J. M. McManus, S. J. Cook, S. Harrold, M. L. Raabe, R. C. Montelaro, and C. J. Issel. 1995. Enhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein. J. Virol. 69:1493-1499[Abstract]. |
| 5a. |
Etemad-Moghadam, B.,
Y. Sun,
E. Nicholson,
G. Karlsson,
D. Schenten, and J. Sodroski.
1999.
Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo.
J. Virol.
73:8873-8879 |
| 6. |
Helseth, E.,
U. Olshevsky,
C. Furman, and J. Sodroski.
1991.
Human immunodeficiency virus type I gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein.
J. Virol.
65:2119-2123 |
| 7. | Hogervorst, E., J. de Jong, A. van Wijk, M. Bakker, M. Valk, P. Nara, and J. Goudsmit. 1995. Insertion of primary syncytium-inducing (SI) and non-SI envelope V3 loops in human immunodeficiency virus type 1 (HIV-1) LAI reduces neutralization sensitivity to autologous, but not heterologous, HIV-1 antibodies. J. Virol. 69:6342-6351[Abstract]. |
| 8. | Joag, S. V., Z. Li, L. Foresman, E. B. Stephens, L.-J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan. 1996. Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. J. Virol. 70:3189-3197[Abstract]. |
| 9. | Kwong, P. D., R. Wyatt, J. Robinson, R. Sweet, J. Sodroski, and W. Hendrickson. 1998. Structure of an HIV-1 gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648-659[CrossRef][Medline]. |
| 10. | Li, A., T. Baba, J. Sodroski, S. Zolla-Pazner, M. Gorny, J. Robinson, M. Posner, H. Katinger, C. Barbas, D. Burton, T.-C. Chou, and R. Ruprecht. 1997. Synergistic neutralization of a chimeric SIV/HIV-1 virus with combinations of human anti-HIV-1 envelope monoclonal antibodies or hyperimmune globulins. AIDS Res. Hum. Retroviruses 13:647-655[Medline]. |
| 11. | Li, J., M. Halloran, C. Lord, A. Watson, J. Ranchalis, M. Fung, N. Letvin, and J. Sodroski. 1995. Persistent infection of macaques with simian-human immunodeficiency viruses. J. Virol. 69:7061-7071[Abstract]. |
| 12. | Li, J., C. I. Lord, W. Haseltine, N. L. Letvin, and J. Sodroski. 1992. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. J. Acquir. Immune Defic. Syndr. 5:639-646. |
| 13. |
Luciw, P. A.,
E. Pratt-Lowe,
K. E. S. Shaw,
J. A. Levy, and C. Cheng-Mayer.
1995.
Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV).
Proc. Natl. Acad. Sci. USA
92:7490-7494 |
| 14. | Means, R. E., T. Greenough, and R. C. Desrosiers. 1997. Neutralization sensitivity of cell culture-passaged simian immunodeficiency virus. J. Virol. 71:7895-7902[Abstract]. |
| 15. |
Montefiori, D. C.,
K. A. Reimann,
M. S. Wyand,
K. Manson,
M. G. Lewis,
R. G. Collman,
J. G. Sodroski,
D. P. Bolognesi, and N. L. Letvin.
1998.
Neutralizing antibodies in sera from macaques infected with chimeric simian-human immunodeficiency virus containing the envelope glycoproteins of either a laboratory-adapted variant or a primary isolate of human immunodeficiency virus type 1.
J. Virol.
72:3427-3431 |
| 16. |
Moore, J. P.,
F. E. McCutchan,
S.-W. Poon,
J. Mascola,
J. Liu,
Y. Cao, and D. D. Ho.
1994.
Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies.
J. Virol.
68:8350-8364 |
| 17. |
Moore, J.,
Q. Sattentau,
H. Yoshiyama,
M. Thali,
M. Charles,
N. Sullivan,
S.-W. Poon,
M. Fung,
F. Traincard,
J. Robinson,
D. D. Ho, and J. Sodroski.
1993.
Probing the structure of the V2 domain of the human immunodeficiency virus type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: the human immune response to the V1 and V2 domains.
J. Virol.
67:6136-6151 |
| 17a. | Moore, J. P., and D. D. Ho. 1995. HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. AIDS 9:S117-S136. |
| 18. | Moore, J. P., and J. Sodroski. 1996. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol. 70:1863-1872[Abstract]. |
| 19. | Moore, J. P., L. A. Wallace, E. A. C. Follett, and J. A. McKeating. 1989. An ELISA for antibodies to the envelope glycoprotein of divergent strains of HIV-1. AIDS 3:155-163[Medline]. |
| 19a. |
Myszka, D.,
R. W. Sweet,
P. Hensley,
M. Brigham-Burke,
P. D. Kwong,
W. A. Hendrickson,
R. Wyatt,
J. Sodroski, and M. Doyle.
2000.
Energetics of the HIV gp120-CD4 binding reaction.
Proc. Natl. Acad. Sci. USA
97:9026-9031 |
| 20. | Parren, P. H. I., J. P. Moore, D. R. Burton, and Q. J. Sattentau. 1999. The neutralizing antibody response to HIV-1: viral evasion and escape from humoral immunity. AIDS 13:S137-S162. |
| 21. | Reimann, K., J. Li, G. Voss, C. Lekutis, K. Tenner-Racz, P. Racz, W. Lin, D. Montefiori, D. Lee-Paritz, R. Collman, J. Sodroski, and N. Letvin. 1996. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. J. Virol. 70:3198-3206[Abstract]. |
| 22. |
Rizzuto, C.,
R. Wyatt,
N. Hernández-Ramos,
Y. Sun,
P. D. Kwong,
W. A. Hendrickson, and J. Sodroski.
1998.
A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding.
Science
280:1949-1953 |
| 23. | Shibata, R., and A. Adachi. 1992. SIV/HIV recombinants and their use in studying biological properties. AIDS Res. Hum. Retroviruses 8:403-409[Medline]. |
| 24. | Speck, R., K. Wehryl, E. Platt, R. Atchison, I. Charo, D. Kabat, B. Chesebro, and M. Goldsmith. 1997. Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop. J. Virol. 71:7136-7139[Abstract]. |
| 25. |
Sullivan, N.,
Y. Sun,
J. Binley,
J. Lee,
C. Barbas,
P. Parren,
D. Burton, and J. Sodroski.
1998.
Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies.
J. Virol.
72:6332-6338 |
| 26. |
Thali, M.,
J. P. Moore,
C. Furman,
M. Charles,
D. D. Ho,
J. Robinson, and J. Sodroski.
1993.
Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.
J. Virol.
67:3978-3988 |
| 26a. | Trkola, A., M. Purtscher, T. Muster, C. Ballaum, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J. Moore, and H. Katinger. 1996. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J. Virol. 70:1100-1108[Abstract]. |
| 27. | Trkola, A., T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. 1996. CD4-dependent, antibody sensitive interactions between HIV-1 and its co-receptor CCR5. Nature 384:184-186[CrossRef][Medline]. |
| 28. |
Ugolini, S.,
I. Mondor,
P. W. H. I. Parren,
D. R. Burton,
S. Tilley,
P. J. Klasse, and Q. J. Sattentau.
1997.
Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization.
J. Exp. Med.
186:1287-1298 |
| 29. | Wu, L., N. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. Cardoso, E. Desjardins, W. Newman, C. Gerard, and J. Sodroski. 1996. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR5. Nature 384:179-183[CrossRef][Medline]. |
| 30. | Wyatt, R., E. Desjardins, V. Olshevsky, C. Nixon, J. Binley, U. Olshevsky, and J. Sodroski. 1997. Analysis of the interaction of the human immunodeficiency virus type 1 gp120 envelope glycoprotein with the gp41 transmembrane glycoprotein. J. Virol. 71:9722-9731[Abstract]. |
| 31. | Wyatt, R., P. D. Kwong, E. Desjardins, R. Sweet, J. Robinson, W. Hendrickson, and J. Sodroski. 1998. The antigenic structure of the human immunodeficiency virus gp120 envelope glycoprotein. Nature 393:705-711[CrossRef][Medline]. |
| 32. | Wyatt, R., J. Moore, M. Accola, E. Desjardins, J. Robinson, and J. Sodroski. 1995. Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J. Virol. 69:5723-5733[Abstract]. |
| 33. |
Wyatt, R.,
N. Sullivan,
M. Thali,
H. Repke,
D. Ho,
J. Robinson,
M. Posner, and J. Sodroski.
1993.
Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions.
J. Virol.
67:4557-4565 |
| 34. |
Wyatt, R.,
M. Thali,
S. Tilley,
A. Pinter,
M. Posner,
D. Ho,
J. Robinson, and J. Sodroski.
1992.
Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.
J. Virol.
66:6997-7004 |
Journal of Virology, December 2000, p. 11955-11962, Vol. 74, No. 24
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