|Human immunodeficiency virus; Capsid; Structure;
|Human immunodeficiency virus type 1 (HIV-1) is the causative
virus responsible for acquired immune deficiency syndrome (AIDS),
for which there is still no protective vaccine. Since 1983, more than 34
million people have been infected with HIV across the world, with 1.5
million people dying as a result of complications from infection each
year. HIV-1 virions mainly infect cells of the immune system and lead
to a gradual reduction in the proportion of CD4+ T cells . This in turn
causes a significant decrease in the patient’s ability to mount an immune
response, and they die as a result of opportunistic infection. HIV-1 thus
remains a major pathogenic threat to human health worldwide.
|The HIV-1 replication cycle resembles that of other retroviruses,
and this knowledge has helped to identify a range of potential targets for
treatment. During the early stages of infection, when a viral particle is
adsorbed to a target cell, the gp120 surface envelope (Env) glycoprotein
binds to the CD4 receptor and either the chemokine receptor-5 (CCR5) or
the CX chemokine receptor-4 (CXCR4) as a co-receptor . Following this,
the Env transmembrane glycoprotein gp41 undergoes a conformational
change that promotes fusion of the viral and cellular membranes . This
process can be stalled by producing a neutralizing antibody that targets
the Env glycoprotein. Likewise, fusion inhibitors can be developed to
target the fusion process before infection. Fusion initiates a cascade of
intracellular events comprising uncoating, reverse transcription, and
integration, and each of these stages of infection offer important antiviral
targets ; for example, the T20 inhibitor is the first FDA-approved fusion
inhibitor for HIV-1/AIDS that works by binding to gp41 [4,5].
|Another class of inhibitors is protease inhibitors, which mainly
block the virus maturation process during the late phase, encompassing
the events that result in virus gene expression, the assembly new virions,
and the release and maturation of infectious virions . Virus assembly
and release are predominantly driven by the Gag polyprotein precursor
[7,8], whereas the maturation process is mediated by proteolysis
events that trigger conformational changes to Gag, thereby converting
immature particles to mature virions. In the immature particles, the Gag
precursors assemble in a radial manner, whereas, in the mature particle,
the viral protease liberates capsid CA proteins from the individual Gag
domains, and these proteins re-assemble to form a conical capsid core
referred to as the fullerene-like capsid .
|There are more than two-dozen drugs approved for clinical use
against HIV, and these drugs are reported to target various critical steps
in the virus replication cycle . Most drugs target the HIV-1 reverse
transcriptase (RT) or protease (PR) enzymes, and, although they show
marked efficacy in the short term, resistance develops rapidly against
these drugs. In 1996, highly active antiretroviral therapy (HAART)
was introduced as a combinatorial approach, and it has remained the
mainstay for HIV-1 therapy. Patients are routinely prescribed two
nucleoside RT inhibitors (NRTIs) along with a protease inhibitor (PI),
a non-nucleoside RT inhibitor (NNRTI) or an integrase strand-transfer
inhibitor (INSTI). Such regimens have turned HIV-1 infection from a
lethal disease into a chronic one that can be managed. If adequately
treated, patient life expectancy can be greatly extended. However,
there are side effects with HAART, and the seemingly unavoidable
emergence of drug-resistant mutant strains with long-term therapy
. Consequently, there is still a need for the development of novel
drugs targeting other molecules in the HIV-1 life cycle.
|The HIV-1 Gag precursor protein is a multi-domain polyprotein,
and its predominant mature product, the CA capsid protein, plays a
multifaceted role during HIV-1 morphogenesis and uncoating .
The advances in our understanding of the structure and function of CA
have made it a promising target for future antiviral intervention .
In this review, we describe these major advancements and discuss the
key interactions involved in core assembly and its structural basis for
current antiviral design.
|The capsid protein, CA
|Structurally, the Gag precursor protein is divided into four
major domains: the N-terminal matrix (MA), the capsid (CA), the nucleocapsid (NC), and the C-terminal p6 (Figure 1A). Two spacer
peptides are located between CA and NC (SP1) and between NC and
p6 (SP2) [8,13]. CA is primarily responsible for the structure of both
the immature Gag lattice and the mature viral core that undergoes
conformational changes. The CA protein comprises 231 aa, and is a
component of three proteins during its lifetime: the full-length p55
(Gag), the precursor p41, and p25, which are proteolytic intermediates.
|The structures of CA and its isolated domains have been solved
by X-ray crystallography and nuclear magnetic resonance (NMR)
spectroscopy [14,15]. The monomer CA contains two independently
folded domains—the N-terminal domain and C-terminal domain
(NTD and CTD, respectively), which are connected by a short flexible
linker (Figure 1B). The NTD (CA residues 1–145) comprises seven
α-helices (CA helices 1–7). Connecting helices 4 and 5 is a prolinerich
loop that binds cyclophilin A [16,17] Studies have shown that
cyclosporine can disrupt the CA–cyclophilin A interaction and inhibit
HIV-1 replication . Similarly, a non-immunosuppressive analog
of cyclosporine, Debio-025, can inhibit early-stage HIV-1 replication,
with higher potency than that exhibited by cyclosporine .
|The CTD (residues 151–231) is composed of a short 310-helix followed by an extended strand and four α-helices (CA helices 8–11). The CA CTD
tends to dimerize through helix 9 on each monomer . Besides, there is
also a novel shoulder-to-shoulder CA dimerization mode mediated by an
S-S bridge . Mutations to residues 184 and 185 (W184A and M185A)
can significantly reduce particle production in cells and CA dimerization
in vitro [22,23]. In helix 8, there is a highly conserved sequence known as
the major homology region (MHR), which plays an important role in Gag
assembly [22,23]. This MHR motif mediates conformational stabilization
of CTD folding. The interface of MHR-swapped CTD  provides an
anti-HIV target for designing compounds that inhibit capsid assembly.
|The immature HIV-1 capsid structure
|HIV-1 assembly proceeds at the plasma membrane when Gag,
which is synthesized in the cytosol, trafficks to the site of assembly. The
CA domain is the main viral determinant driving Gag assembly. The
Gag protein packages the full‐length genomic RNA into the nascent,
immature virus particle together with the GagPol precursor. The
structure of the intact, full‐length Gag precursor is still unclear, owing to
large size of Gag and the presence of flexible interdomain connections.
Cryoelectron microscopy (cryo-EM) and cryoelectron tomography
(cryo-ET) of the immature virus particle show that Gag molecules are aligned and packaged radially (Figure 1A), with the MA domain bound
to the inner leaflet of the viral membrane and the C-terminal region of
Gag oriented toward the center of the particle .
|The Gag subunits in the immature structure are organized as a
lattice of hexamers, with a spacing of 8 nm, and this arrangement forms
an intermediate layer of cup-shaped structures, each made (from top to
bottom) from a hollow hexameric ring of NTD domains, a hexameric
ring of CTD domains, and a stem formed by six SP1 segments .
Previous structural analyses suggest that Gag hexamers are stabilized
mainly by a six-helix bundle of SP1 peptides and CTD–CTD
interactions, whereas the hexamers are linked to one another mainly
through NTD–NTD and CTD–CTD homodimerization at interfaces.
The immature Gag lattice is continuous but incomplete to accommodate
the curvature necessary to form a particle with a diameter of ~120 nm.
|Because the structure of the immature Gag lattice is curved and
flexible, it has been technically more challenging to define. Recent
breakthroughs in both the hardware and software algorithms required
for cryo‐EM and cryo‐ET have facilitated improved HIV-1 structural analyses. Bharat et al. combined cryo‐EM and cryo‐ET and were able
to solve the structure of the immature Gag lattice in in vitro‐assembled
tubes formed by a truncated version of the betaretrovirus Mason‐
Pfizer monkey virus (MPMV) Gag protein . The 8-Å resolution
structure permitted the derivation of a pseudo-atomic model of CA
in the immature retrovirus, and this led to the discovery that CA–CA
contacts in the immature Gag lattice differ from those in the mature
CA lattice. Later work by the group revised the MPMV-based model by
applying cryo-ET and sub-tomogram averaging methods to resolve the
structure of the capsid lattice within intact immature HIV-1 particles
at subnanometre resolution . The resulting model demonstrates
that the quaternary structural interactions mediating HIV-1 assembly
differ substantially from that of the MPMV CA proteins. Although the
observed electron densities show the SP1 assembles a six-helix bundle
consistent with previous models, the precise structure of SP1 is not
resolved. Early studies provided evidence that the CA–SP1 cleavage
site is the binding site for HIV-1 maturation inhibitors. Bevirimat
(BVM), which blocks the CA–SP1 cleavage site , is the first Gagtargeted
compound to reach clinical trials (Table 1); however, its exact mechanism of action is not well-defined . Further studies will be
required to obtain the structure of the CA–SP1 boundary region in the
context of the assembled, immature Gag, and this insight will help to
determine the precise location of the Bevirimat binding site.
|The mature HIV-1 capsid structure
|The mature capsid structure is well-defined. During protease
processing of the mature Gag, the capsid undergoes a major change in
virion morphology. Unlike the immature structure, the CA subunits in
the mature structure are organized as a lattice of hexamers with 10-nm
spacing. As mentioned earlier, the mature capsid resembles a fullerene
cone, with the hexameric lattice closed off by seven pentamers at its
wide end and five at its narrow end (Figure 1D) . There are three
different interfaces for the CA–CA interaction in the mature capsid:
(i) the NTD–NTD interface between NTD domains in the hexamers;
(ii) the NTD–CTD interface between the NTD and CTD domains
belonging to neighboring subunits of the same hexamer; (iii) the
CTD–CTD interface between CTD domains belonging to neighboring
hexamers. These three inter-subunit interfaces have been resolved at
the atomic level by X-ray crystallography and cryo-EM [15,32].
|HIV-1 CA spontaneously polymerizes into capsid-like particles in
vitro, and therefore it does not form hexamers or pentamers in solution.
To overcome this problem, Pornillos et al. introduced disulfide bridges at the NTD–NTD interface to crosslink the monomers and stabilize the
hexamer (Figures 1C and 1F) or pentamer (Figures 1E and 1G). They
also introduced mutations to two residues—W184A and M185A—at
the CTD–CTD interface to weaken the CA–CA dimerization [33-35].
The group then went on to solve the atomic structures of the hexamers
and pentamers by X-ray crystallography. Zhao et al reported the mature
HIV-1 capsid structure at 8-Å resolution by cryo-EM and using allatom
molecular dynamics (Figure 1D) . The resolved structure
showed a three-helix bundle with critical hydrophobic interactions
at the CTD trimer interface; further mutation analysis indicated that
this bundle played a critical role in the assembly and stability of the
mature capsid. The complete atomic HIV-1 capsid model provided a
basis to further study capsid function and identifies targets that were
appropriate for pharmacological intervention.
|More recent X-ray crystallography findings of the native HIV-1
capsid protein have revealed conformational variability . This higherresolution
native CA structure demonstrates interactions between CA
monomers, with six-fold symmetry within hexamers (intrahexamer),
and three- and two-fold symmetry between neighboring hexamers
(inter-hexamer). The results also show hydrophilic, water-mediated
interactions, the disruption of which alters these inter-hexameric
interfaces. These new insights bring a clearer picture of HIV-1 biology
and will aid in the design of better antiretroviral drugs. However,
the HIV-1 assembly mechanism itself remains unclear, and future work should be aimed at determining how the immature CA lattice
disassembles and reassembles to form the mature CA lattice.
|CA as a target of antivirals
|The HIV-1 capsid protein plays a central role in the virus replication
cycle, making it an attractive target for the development of anti‐
HIV‐1 inhibitors (Table 1). Disruption of CA–CA contacts by specific
compounds could be used to block the assembly of immature particles
or the mature capsid core. An early small‐molecule inhibitor, CAP-1,
was identified by Summers and colleagues with an in silico screening
approach . NMR and X-ray crystallographic studies showed that
CAP-1 binds to a pocket formed at the point at which helices 1, 2, 4 and
7 of the NTD interact (Figure 2A) . This interaction disrupts virus
assembly and maturation, and this pocket is also the binding site for
other small molecules, such as β-defensin 3 and benzimidazole-4 .
|The CTD-binding peptide CAI (ITFEDLLDYYGP) was screened by
phage display. This peptide inhibits both immature and mature capsid
assembly in vitro. Structure analysis of the CAI–CTD complex showed
that the peptide binds to a hydrophobic groove formed by CA helices
8, 9 and 11 (Figure 2B) . CAI binding to the CTD causes steric
interference, limiting the formation of the native NTD–CTD interface
between CA subunits in the mature capsid hexamers. Furthermore, the
binding also induces a conformational rearrangement of the CTD dimer,
which destabilizes the CTD dimerization interface between hexamers
. To improve the affinity of CAI for the CTD and to enhance its cellpenetrating
ability, CAI derivatives were developed using hydrocarbon
stapling. Two of these derivatives, NYAD-1 (ITFXDLLXYYGKKK) and
NYAD-13 (ITFLDLLLYYGKKK), have been shown to inhibit HIV-1
infection ex vivo and display a broad spectrum of antiviral activity .
|The compound PF‐3450074 (also known as PF74) is the bestcharacterized
small‐molecule inhibitor targeting the viral CA protein
. Structure analyses indicate that PF74 makes contacts with the
HIV-1 CA hexamer at the NTD–CTD interface, binding with higher
affinity to the intact hexamer than to monomeric CA. The R1 and
R2 aromatic groups of PF74 occupy the hydrophobic pocket formed
by HIV-1 CA-NTD helices 3, 4, 5 and 7. Meanwhile, the R3 indole
interacts with CTD in the hexamer-bound form (Figure 2C). Blair
and colleagues speculated that PF74 specifically targets the assembled
capsid, rather than the unassembled CA subunit. PF74 exerts inhibition
over normal capsid assembly and disassembly in the early and late
phasess of HIV infection. PF74 was found to accelerate CA assembly
in HIV-1 CA multimerization assay . However, the treatment over
viral cores isolated from HIV-1 virion/pseduoviron with PF74 can
destabilize the mature capsid . The findings imply that PF74 might
function in different events of CA assembly or disassembly throughout
the virus life cycles.
|Recent studies have uncovered the more nuanced mechanism
of action of this compound: (1) At higher concentrations, PF74
destabilizes viral core. And at lower concentrations, potent inhibition
is retained because it competes with the binding of two host factors,
nuclear pore complex protein 153 (NUP153) and cleavage and polyadenylation
specificity factor 6 (CPSF6) . (2) The reported cocrystal
structure shows PF74 targets the same binding pocket in the
assembled CA as those of CPSF6 and NUP153 . Thus, PF74 might
implement antiviral activity by blocking CA from binding with the two
host factors. (3) A new crystal structure of native CA suggests that PF74
might affect the capsid stability by inducing subtle changes at the interhexamer
|The Boehringer Ingelheim group identified two classes of compounds, benzodiazepines (BD) and benzimidazoles (BM) . BD
and BM target to CA NTD with the binding sites similar as that of CAP-
1, and otherwise exhibit higher antiviral activity. Another compound
named BI-1 interacts with CA NTD on binding sites overlapping with
that of PF74, but presents distinct functional mode in the antiviral
research . All the antiviral reagents mentioned in this review were
listed in Table 1 with the information of structure, antiviral mechanism
and research stage.
|Although numerous inhibitors targeting the capsid have been
identified to date, they have not yet to be successfully exploited in
clinically approved antiviral therapies. It is likely that resistance to the
current anti-HIV-1 drugs will become an increasing problem in the
near future, and this will necessitate the development of novel drugs. We
believe that the HIV-1 capsid will become a promising target because
of its important function in the HIV-1 life cycle. In recent years, we
have witnessed remarkable advances in our understanding of HIV-1
immature and mature capsid structures, and we have gained insight into
the important function of the capsid protein in the replication cycle.
However, many questions remain to be fully answered. For example,
what is the structure of the CA–SP1 boundary region in the assembled
Gag lattice, and how do maturation inhibitors bind to this region? How
does the immature CA lattice disassemble and reassemble to form the
mature CA lattice? Exploring the structure–function relationship of
the capsid in answering these questions will help to drive CA‐targeted
|The work was supported by National Natural Science Foundation (Grant no.
- Swanstrom R, Coffin J (2012) HIV-1 pathogenesis: the virus. Cold Spring HarbPerspect Med 2: a007443.
- Freed EO (2001) HIV-1 replication. Somat Cell Mol Genet 26: 13-33.
- Wilen CB, Tilton JC, Doms RW (2012) HIV: cell binding and entry. Cold Spring HarbPerspect Med 2.
- Fassati A (2012) Multiple roles of the capsid protein in the early steps of HIV-1 infection. Virus Res 170: 15-24.
- Chong H, Qiu Z, Su Y, Yang L, He Y (2015) Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket. AIDS 29: 13-21.
- Freed EO (2015) HIV-1 assembly, release and maturation. Nat Rev Microbiol 13: 484-496.
- Ganser-Pornillos BK, Yeager M, Sundquist WI (2008) The structural biology of HIV assembly. CurrOpinStructBiol 18: 203-217.
- Bell NM, Lever AM (2013) HIV Gag polyprotein: processing and early viral particle assembly. Trends Microbiol 21: 136-144.
- Ganser-Pornillos BK, Yeager M, Pornillos O (2012) Assembly and architecture of HIV. AdvExp Med Biol 726: 441-465.
- Arts EJ, Hazuda DJ (2012) HIV-1 antiretroviral drug therapy. Cold Spring HarbPerspect Med 2: a007161.
- Campbell EM, Hope TJ (2015) HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat Rev Microbiol 13: 471-483.
- Blair WS, Pickford C, Irving SL, Brown DG, Anderson M, et al. (2010) HIV capsid is a tractable target for small molecule therapeutic intervention. PLoSPathog 6: e1001220.
- Tedbury PR, Freed EO (2015) HIV-1 gag: an emerging target for antiretroviral therapy. Curr Top MicrobiolImmunol 389: 171-201.
- Ganser-Pornillos BK, Cheng A, Yeager M (2007) Structure of full-length HIV-1 CA: a model for the mature capsid lattice. Cell 131: 70-79.
- Byeon I-JL, Meng X, Jung J, Zhao G, Yang R, et al. (2009) Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139: 780-790.
- Gamble TR, Vajdos FF, Yoo S, Worthylake DK, Houseweart M, et al. (1996) Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 87: 1285-1294.
- Cortines JR, Lima LM, Mohana-Borges R, Millen Tde A, Gaspar LP, et al. (2015) Structural insights into the stabilization of the human immunodeficiency virus type 1 capsid protein by the cyclophilin-binding domain and implications on the virus cycle. BiochimBiophysActa 1854: 341-348.
- Luban J (2007) Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J Virol 81: 1054-1061.
- Daelemans D, Dumont JM, Rosenwirth B, De Clercq E, Pannecouque C (2010) Debio-025 inhibits HIV-1 by interfering with an early event in the replication cycle. Antiviral Res 85: 418-421.
- Ivanov D, Tsodikov OV, Kasanov J, Ellenberger T, Wagner G, et al. (2007) Domain-swapped dimerization of the HIV-1 capsid C-terminal domain. ProcNatlAcadSci U S A 104: 4353-4358.
- Gu Y, Cao F, Wang L, Hou W, Zhang J, et al. (2013) Structure of a novel shoulder-to-shoulder p24 dimer in complex with the broad-spectrum antibody A10F9 and its implication in capsid assembly. PLoS One 8: e61314.
- Purdy JG, Flanagan JM, Ropson IJ, Rennoll-Bankert KE, Craven RC (2008) Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly. J Virol 82: 5951-5961.
- Chang YF, Wang SM, Huang KJ, Wang CT (2007) Mutations in capsid major homology region affect assembly and membrane affinity of HIV-1 Gag. J MolBiol 370: 585-597.
- Bocanegra R, Fuertes MÁ, Rodríguez-Huete A, Neira JL, Mateu MG (2015) Biophysical analysis of the MHR motif in folding and domain swapping of the HIV capsid protein C-terminal domain. Biophys J 108: 338-349.
- Briggs JA, Riches JD, Glass B, Bartonova V, Zanetti G, et al. (2009) Structure and assembly of immature HIV. ProcNatlAcadSci U S A 106: 11090-11095.
- Wright ER, Schooler JB, Ding HJ, Kieffer C, Fillmore C, et al. (2007) Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26: 2218-2226.
- Bharat TA, Davey NE, Ulbrich P, Riches JD, de Marco A, et al. (2012) Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy. Nature 487: 385-389.
- Schur FK, Hagen WJ, Rumlová M, Ruml T, Müller B, et al. (2015) Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution. Nature 517: 505-508.
- Nguyen AT, Feasley CL, Jackson KW, Nitz TJ, Salzwedel K, et al. (2011) The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles. Retrovirology 8: 101.
- Keller PW, Adamson CS, Heymann JB, Freed EO, Steven AC (2011) HIV-1 maturation inhibitor bevirimat stabilizes the immature Gag lattice. J Virol 85: 1420-1428.
- Briggs JA, Grünewald K, Glass B, Förster F, Kräusslich HG, et al. (2006) The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions. Structure 14: 15-20.
- Mateu MG (2009) The capsid protein of human immunodeficiency virus: intersubunit interactions during virus assembly. FEBS J 276: 6098-6109.
- Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, et al. (2009) X-ray structures of the hexameric building block of the HIV capsid. Cell 137: 1282-1292.
- Pornillos O, Ganser-Pornillos BK, Banumathi S, Hua Y, Yeager M (2010) Disulfide bond stabilization of the hexamericcapsomer of human immunodeficiency virus. J MolBiol 401: 985-995.
- Pornillos O, Ganser-Pornillos BK, Yeager M (2011) Atomic-level modelling of the HIV capsid. Nature 469: 424-427.
- Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, et al. (2013) Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497: 643-646.
- Gres AT, Kirby KA, KewalRamani VN, Tanner JJ, Pornillos O, et al. (2015) STRUCTURAL VIROLOGY. X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability. Science 349: 99-103.
- Tang C, Loeliger E, Kinde I, Kyere S, Mayo K, et al. (2003) Antiviral inhibition of the HIV-1 capsid protein. J MolBiol 327: 1013-1020.
- Kelly BN, Kyere S, Kinde I, Tang C, Howard BR, et al. (2007) Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein. J MolBiol 373: 355-366.
- Lemke CT, Titolo S, von Schwedler U, Goudreau N, Mercier JF, et al. (2012) Distinct effects of two HIV-1 capsid assembly inhibitor families that bind the same site within the N-terminal domain of the viral CA protein. J Virol 86: 6643-6655.
- Ternois F, Sticht J, Duquerroy S, Kräusslich HG, Rey FA (2005) The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat StructMolBiol 12: 678-682.
- Barklis E, Alfadhli A, McQuaw C, Yalamuri S, Still A, et al. (2009) Characterization of the in vitro HIV-1 capsid assembly pathway. J MolBiol 387: 376-389.
- Zhang H, Zhao Q, Bhattacharya S, Waheed AA, Tong X, et al. (2008) A cell-penetrating helical peptide as a potential HIV-1 inhibitor. J MolBiol 378: 565-580.
- Shi J, Zhou J, Shah VB, Aiken C, Whitby K (2011) Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J Virol 85: 542-549.
- Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S, et al. (2014) Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly. PLoSPathog 10: e1004459.
- Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, et al. (2014) Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. ProcNatlAcadSci U S A 111: 18625-18630.
- Lamorte L, Titolo S, Lemke CT, Goudreau N, Mercier JF, et al. (2013) Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Antimicrob Agents Chemother 57: 4622-4631.