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At least 19 recordsLinked to original sources

PubMed1993

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.

Amino Acid Sequence↗

PubMed1989

Antibody-dependent cellular cytotoxicity is directed against both the gp120 and gp41 envelope proteins of HIV.

To define the target antigens for antibody-dependent cellular cytotoxicity (ADCC), assays were performed using affinity-purified human immunoglobulin (Ig) or polyclonal rabbit sera directed against specific proteins of HIV. ADCC was not found using affinity-purified anti-core (p25) human Ig or sera obtained from rabbits hyper-immunized with recombinant p25. However, when affinity-purified human Ig or rabbit antisera specific for the envelope glycoproteins, gp120 or gp41, were used in ADCC assays, killing of HIV-infected cells was observed. These results indicate that antibodies in the infected individual that mediate ADCC are directed against both the gp120 and gp41 HIV envelope proteins and not against the viral core protein.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1995

An approach for an immunoaffinity AIDS sensor using the conservative region of the HIV envelope protein (gp41) and its monoclonal antibody.

A monoclonal antibody for the conservative region of gp41, which is one of the HIV envelope proteins, was produced. The antigen determining site of gp41 was examined using the epitope mapping technique, followed by an enzyme linked immunosorbent assay. Some peptides had comparable affinities for the monoclonal antibody, but the peptide EGIEE, having a slightly weaker immunoaffinity than gp41, was the most preferable for the construction of an immunoaffinity AIDS sensor. For the detection of gp41, EGIEE was labelled with catalase and used as a mimic antigen; it was bound to the antibody present on an immuno-membrane and, due to the replacement reaction of the mimic antigen by gp41, indirect quantitative measurement of gp41 was possible using an oxygen electrode. Anti-gp41 antibody was also detected using a mimic antibody, which was chemically modified with polyethylene glycol. An immunoaffinity AIDS sensor was constructed using the mimic molecules which were tailored to have a suitable immunoaffinity for HIV antigen and/or antibody.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Interaction of a basic amphipathic peptide from the carboxyterminal part of the HIV envelope protein gp41 with negatively charged lipid surfaces.

The interaction of the positively charged synthetic amphipathic peptide fragment gp41(828) corresponding to a segment from the carboxyterminal region of the HIV envelope glycoprotein gp41 with lipid monolayers spread at the air-water interface has been studied by film balance measurements. The peptide itself does not form a stable monolayer but interacts with phospholipids spread together on the aqueous surface. Upon compression of a mixed phosphatidylcholine-peptide monolayer the peptide is irreversibly squeezed out of the lipid-peptide monolayer. In contrast, with negatively charged phosphatidylglycerol stable lipid-peptide monolayers are formed even in the presence of up to 30 mol% peptide. The monolayer may be expanded and compressed repeatedly without significant loss of substance. After addition of calcium ions to the subphase of a phosphatidylglycerol-peptide monolayer the peptide is to some extent excluded from the monolayer. In contrast to phosphatidylcholine monolayers this process is partly reversible and the excluded material is reincorporated into the film during subsequent expansion. We conclude that attached to the headgroups of the lipid monolayer a peptide-layer stabilized at the surface by electrostatic interactions is formed. The surface action may lead to rigidified lipid-peptide domains causing an increased membrane permeability which might correspond to a cytopathologic function of the protein fragment.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

The effect of lipid composition and physical state of phospholipid monolayer on the binding and incorporation of a basic amphipathic peptide from the C-terminal region of the HIV envelope protein gp41.

The interaction of a peptide identical to the carboxy terminal region of the envelope glycoprotein gp41(828) of HIV with negatively charged phospholipids in a monolayer was studied by a Wilhelmy film balance. No significant interaction of the peptide with a monolayer composed of pure neutral but a strong affinity to negatively charged phospholipids could be observed. In mixed phospholipid monolayers the binding of the gp41(828) is primarily limited by the amount of acidic phospholipids. The physical state of the monolayer is another important parameter for binding. Clustering of negatively charged phospholipids and the surface pressure are crucial. Ca(2+) ions strongly interfere with the peptide-lipid interaction up to complete abolishment. The effects observed are dependent on the nature of the acidic lipid. Phosphatidylglycerol was found to be more sensitive than phosphatidylserine. The significance of the results for processes like virus assembly and budding will be discussed.

Amino Acid Sequence↗

PubMed1998

Antigenic characterization of HIV-1 gp41 binding proteins.

The envelope protein HIV-1 gp41 has been shown to exert various effects on human T-cells, B-cells and monocytes like inhibition of cell proliferation, modulation of MHC expression and cytokine production. In contrast to gpl20, where several receptor molecules have been identified, the receptor for gp41 is still unknown. Using a sepharose column, coupled with recombinant soluble gp41, (rsgp41; Env amino acids 539-684), five gp41-binding proteins of 37, 45, 50, 62 and 100 kDa had been isolated from lysates of the B-cell line Raji. Two mouse antiserums were generated against the proteins P45 and P62 and were tested against the binding specificity of both antiserums. In Western blot analysis the antiserums recognized two protein bands of 45 and 62 kDa in complete Raji cell lysates, as well as the purified proteins P45 and P62, respectively, but did not show any cross-reaction, indicating that the two proteins do not share any immunological epitopes. Besides, the polyclonal antiserums did not recognize the other gp41-binding proteins P37, P50 and P100. Using the P62 antiserum proteins of the same size as in Raji cell lysates were stained in the lysates of the monocytic cell line U937 and the T-cell line H9, demonstrating distribution of P62 in different blood cells. P45 seems not to be identical to HLA-C which had been shown to bind to gp41. These results indicate, that P45 and P62 are two separate gp41-binding proteins without homology to each other or to the other gp41-binding proteins.

Animals↗

PubMed1989

Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein.

Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic alpha-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772-790) and gp41(828-848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as alpha-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel alpha-helices of segments 770-794 and 824-856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with alpha-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770-856, with the loop closed by membrane-associated amphipathic alpha-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.

Amino Acid Sequence↗

PubMed1995

Human complement proteins C3b, C4b, factor H and properdin react with specific sites in gp120 and gp41, the envelope proteins of HIV-1.

Recently we reported the basic phenomenon of an interaction between the envelope glycoproteins of HIV-1 gp120 and gp41 and components of the human complement system, i.e. activated C4 (C4b) and activated C3 (C3b) and the complement regulator proteins factor H and properdin. In this study we analyze these interactions in detail. Using 46 overlapping peptides of gp120 attached to microtiter plates, binding of activated human C3 to 6 regions in gp120 was found (aa 100-129, 161-190, 231-250, 301-328, 410-449, 470-499). In competition assays with soluble peptides, representatives of four of these regions were capable to partially inhibit C3b binding to immobilized gp120. Activated human C4 interacted only with peptides covering aa 410-449, but both in direct binding assays and fluid phase inhibition studies. The multi-reactivity of gp120 with C3b was also supported by the fact that gp120 agglutinated erythrocytes coated with C3b. Guided by partial aa sequence homology of gp120 and human C4b binding protein (C4bp) as well as human properdin we detected binding of anti-properdin to aa 100-129 in gp120 and of anti-C4bp to aa 410-449 in gp120. This cross-reactivity was also confirmed by a monoclonal antibody directed against aa 416-443 of gp120, which could be shown to bind C4bp. Interestingly, aa 310-328, part of the V3-loop, were found to show an aa sequence similarity to human complement receptor type 3 (alpha-chain). Consequently, of the 4 (or possibly 6) interaction sites of gp120 with activated human C3, 3 may bind due to imitation of either properdin, CR3 or C4bp. In addition to C4b and C3b, we detected interaction of factor H with gp120; it selectively bound to aa 102-129. Using 14 overlapping peptides of gp41 attached to plates, we identified 4 areas in gp-41 (aa 561-585, 587-605, 615-635, 651-675) which bound human factor H. All of them except the first region partially inhibited factor H binding to gp41 in competition assays with soluble peptides. Properdin bound only to 2 regions (aa 584-614, 651-675). The first 3 sites in gp41 were already shown by us to share homology to sites in human C3. The region around aa 651-675 now also turned out to be similar to human C3. These data demonstrate that the interaction of both, gp120 and gp41, with the complement system is polyvalent and complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed2000

N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes.

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. In this study we show that N36, a synthetic peptide derived from the N-terminus of gp41, induced directional migration and calcium mobilization in human monocytes and neutrophils. The activity of N36 on phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled seven-transmembrane receptor(s). Since high concentrations of the bacterial chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low-affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host immune cells through FPRL1. Since the activation of FPRL1 in monocytes has been shown to heterologously desensitize chemokine receptors, the reduced phagocyte response to chemoattractants seen in AIDS patients may be attributed, at least in part, to heterologous desensitization.

Anti-HIV Agents↗

PubMed1998

Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target.

Synthetic C peptides, corresponding to the C helix of the HIV type 1 (HIV-1) gp41 envelope protein, are potent inhibitors of HIV-1 membrane fusion. One such peptide is in clinical trials. The crystal structure of the gp41 core, in its proposed fusion-active conformation, is a trimer of helical hairpins in which three C helices pack against a central coiled coil. Each C helix shows especially prominent contacts with one of three symmetry-related, hydrophobic cavities on the surface of the coiled coil. We show that the inhibitory activity of the C peptide C34 depends on its ability to bind to this coiled-coil cavity. Moreover, examining a series of C34 peptide variants with modified cavity-binding residues, we find a linear relationship between the logarithm of the inhibitory potency and the stability of the corresponding helical-hairpin complexes. Our results provide strong evidence that this coiled-coil cavity is a good drug target and clarify the mechanism of C peptide inhibition. They also suggest simple, quantitative assays for the identification and evaluation of analogous inhibitors of HIV-1 entry.

Amino Acid Sequence↗

PubMed1995

Interaction of several complement proteins with gp120 and gp41, the two envelope glycoproteins of HIV-1.

OBJECTIVE: To study the binding of human complement proteins to gp41 and gp120 of HIV-1. METHODS: The interaction of complement proteins with gp41 and gp120 and their effect on the gp41-gp120 complex in enzyme-linked immunosorbent assays (ELISA) and on stably transfected Schneider-2 cells expressing a gp41-gp120 complex was investigated. The molecular basis of these interactions was analysed by computer-supported sequence analysis. RESULT: gp41 strongly binds human complement regulatory proteins factors H and properdin, and weakly binds factors I and B. The binding occurs with recombinant soluble (rs) gp41 fixed on ELISA plates as well as gp41-gp120 complex expressed on Schneider-2 cells. The basis for this binding potential might be an amino-acid (aa) sequence of gp41 displaying homologies to sites in human C3. rgp120 also binds C3(H2O), a C3b-like form of C3, and C4b. These binding features of gp120 can be explained by homology of constant region (CR) 4 in gp120 to sites in C4b binding protein. Additionally, CR1 in gp120 exhibits a weak similarity to human properdin. Preincubation of rsgp41 with either factor H or properdin, and of rgp120 with C3b or C4b affected the interaction between rsgp41 and rgp120. Incubation of Schneider-2 cells, expressing a functional gp41-gp120 complex, with factor H reduced the detectable amount of gp120. This effect was similar to that induced by soluble CD4. CONCLUSION: These results strongly suggest that HIV-1 envelope proteins interact with human complement proteins. Additionally, C3b-like features of gp41 and the C3b/C4b binding structures in gp120 may affect the non-covalent association between gp41 and gp120.

Amino Acid Sequence↗

PubMed2001

Structure and interaction with membrane model systems of a peptide derived from the major epitope region of HIV protein gp41: implications on viral fusion mechanism.

The HIV-1 gp41 envelope protein mediates entry of the virus into the target cell by promoting membrane fusion. With a view toward possible new insights into viral fusion mechanisms, we have investigated by infrared, fluorescence, and nuclear magnetic resonance spectroscopies and calorimetry a fragment of 19 amino acids corresponding to the immunodominant region of the gp41 ectodomain, a highly conserved sequence and major epitope. Information on the structure of the peptide both in solution and in the presence of model membranes, its incorporation and location in the phospholipid bilayer, and the modulation of the phase behavior of the membrane has been gathered. Here we demonstrate that the peptide binds and interacts with negatively charged phospholipids, changes its conformation in the presence of a membraneous medium, and induces leakage of vesicle contents as well as a new phospholipid phase. These characteristics might be important for the formation of the fusion-active gp41 core structure, promoting the close apposition of the two viral and target-cell membranes and therefore provoking fusion.

Amino Acid Sequence↗

PubMed2000

HIV-1 envelope protein gp41 modulates expression of interleukin-10 and chemokine receptors on monocytes, astrocytes and neurones.

OBJECTIVE: To analyse the effect of HIV-1 transmembrane protein gp41 on cytokine production and chemokine receptor expression in blood and brain. DESIGN: Because previous results had demonstrated that recombinant gp41 contributes to HIV-induced dysfunction of blood immune cells we investigated its effect on interleukin (IL)-10 synthesis and expression of the HIV coreceptors CCR5 and CXCR4 in different human brain cells. METHODS: Astrocytic, microglial and neuronal cell lines were incubated with the extracellular domain of gp41 (aa565-647). Secretion of IL-10 into the medium was measured by ELISA. Chemokine receptor expression was analysed by fluorescence activated cell sorting and by RT-PCR. RESULTS: Incubation of the astrocytic cell line U87 with gp41 induced more than a 10 fold up-regulation of IL-10 secretion. This modulation was shown to be time- and dose-dependent. Use of inhibitors for different signal transduction pathways indicated a similar transduction cascade for the alteration of IL-10 production in astrocytes as in monocytes with participation of cAMP/adenylate cyclase and activation of p70S6 kinase. To a lesser extent IL-10 synthesis was also up-regulated by gp41 in the neuronal cell line SK-N-SH. In all cell types up-regulation of IL-10 paralleled by an enhanced expression of the chemokine receptor and HIV-1 coreceptor CCR5. This up-regulation was driven by IL-10 as shown by use of an IL-10 antibody. Expression of the chemokine receptor CXCR4 was only slightly altered. CONCLUSIONS: These findings suggest a role for gp41 in the modulation of brain-specific host defence, cell migration and cell infectivity by HIV.

Astrocytes↗

PubMed2002

Recombinant envelope protein of HIV-1 subtype E as antigen in HIV-1 antibody detection enzyme immunoassay.

In order to develop a reliable and inexpensive serodiagnostic method to be used for anti-HIV antibody detection in Thailand, recombinant envelope (TM or gp41 subunit) protein of HIV-1 subtype E was produced from prokaryotic cell (Escherichia coli) as the source of antigen in enzyme immunoassay (TE diagnostic EIA kit). HIV-1 gp41 subunit of subtype E was successfully expressed in E. coli in the form of polyhistidine-tagged proteins, comprising of rgp41A (601 bases N-terminal half of TM or 25kDa) and rgp41B (560 bases C-terminal half of TM or 24 kDa) by using an expression vector, pBAD/His C. The amount of protein, dilution of sera, and anti-human IgG labeled HRP used in the EIA test optimized by a checker board titration of the protein and seropositive or seronegative sera, were 5.0 microg/ml, 1:300, and 1:4,000, respectively. The blinded test evaluation of TE-diagnostic EIA in 500 seropositive and 500 seronegative sera which have been simultaneously tested by two available commercial kits and compared with our TE diagnostic EIA, gave 99.6% sensitivity and specificity. The other known genetic subtypes sera such as subtype A (n=5), B (n=9), C (n=4) and D (n=5) were also positive with this EIA. The estimated manufacturer cost per test of rgp41 based anti-HIV antibody detection EIA or TE-diagnostic EIA was about 15 baht. This recombinant envelope (gp41 or TM) protein from HIV-1, which can be produced in large quantities without any hazards from growing the virus and has lower cost to produce anti-HIV antibody serological diagnostic kit, should be considered as an HIV screening test in Thailand.

Base Sequence↗

PubMed2000

Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41.

The novel virucidal protein cyanovirin-N (CV-N) binds with equally high affinity to soluble forms of either H9 cell-produced or recombinant glycosylated HIV-1 gp120 (sgp120) or gp160 (sgp160). Fluorescence polarization studies showed that CV-N is also capable of binding to the glycosylated ectodomain of the HIV-envelope protein gp41 (sgp41) (as well as SIV glycoprotein 32), albeit with considerably lower affinity than the sgp120/CV-N interaction. Pretreatment of CV-N with either sgp120 or sgp41 abrogated the neutralizing activity of CV-N against intact, infectious HIV-1 virions. Isothermal calorimetry and optical biosensor binding studies showed that CV-N bound to recombinant sgp120 with a K(d) value ranging from 2 to 45 nM and to sgp41 with a K(d) value of 606 nM; furthermore, they indicated an approximate 5:1 stoichiometry for CV-N binding to sgp120 and a 1:1 stoichiometry for CV-N binding to sgp41. Circular dichroism studies additionally illuminated the binding of CV-N with both sgp120 and sgp41, providing the first direct evidence that conformational changes are a consequence of CV-N interactions with both HIV-1 envelope glycoproteins.

Anti-HIV Agents↗

PubMed1994

The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS.

The human immunodeficiency virus (HIV) gp120 and gp41 envelope proteins and Staphylococcus aureus protein A (SPA) all have Fc receptor (FcR)-like immunoglobulin binding factor (IBF) activity for the Fc constant fragments of human immunoglobulin G (IgG). Viral IBF may contribute to the pathology of HIV by jamming the network of FcR signals that control FcR-dependent immunity. Conversely, the bacterial IBF SPA has anti-retroviral activity that may involve antagonism of the immunopathological action of viral IBF, strongly suggesting IBF may act as a double-edged sword that might be turned against viral invaders.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Improved separation of integral membrane proteins by continuous elution electrophoresis with simultaneous detergent exchange: application to the purification of the fusion protein of the human immunodeficiency virus type 1.

We describe a protocol for preparative-scale purification of the fusion protein of the human immunodeficiency virus type 1 (HIV-1), gp41, from cells overexpressing the viral envelope proteins and from HIV-1 isolates. In the first step, the proteins were extracted from the membrane in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample buffer. The extract was then subjected to separation by continuous elution electrophoresis using a nonionic or zwitterionic detergent in the mobile elution buffer, which results in the simultaneous exchange of SDS with that detergent. The separated proteins were obtained in an SDS-free buffer containing either Brij, 3-[(3-chloramidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or Triton X-100 and could then be subjected to subsequent purification steps like isoelectric focusing in the second dimension or immunoaffinity chromatography. The dilute protein fraction was concentrated and applied on a 10 mL immunoaffinity column packed with anti-gp41 monoclonal antibody immobilized on protein-G sepharose. The protein was eluted from the column at pH 2.7 and obtained in pure form in amounts of 30-50 micrograms that constituted a yield of 1%. The pure gp41 could not be sustained in solution in the absence of detergent and was not susceptible to proteolytic digestion by trypsin. The identification of the protein and the degree of purity was confirmed indirectly using surface enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The possible application of this approach for the isolation of integral membrane proteins with the propensity to undergo spontaneous folding and aggregation is being discussed.

Chromatography, Affinity↗

PubMed2000

Biophysical characterization of gp41 aggregates suggests a model for the molecular mechanism of HIV-associated neurological damage and dementia.

In human immunodeficiency virus (HIV)-infected individuals, the level of the HIV envelope protein gp41 in brain tissue is correlated with neurological damage and dementia. In this paper we show by biochemical methods and electron microscopy that the extracellular ectodomain of purified HIV and simian immunodeficiency virus gp41 (e-gp41) forms a mixture of soluble high molecular weight aggregate and native trimer at physiological pH. The e-gp41 aggregate is shown to be largely alpha-helical and relatively stable to denaturants. The high molecular weight form of e-gp41 is variable in size ranging from 7 to 70 trimers, which associate by interactions at the interior of the aggregate involving the loop that connects the N- and C-terminal helices of the e-gp41 core. The trimers are predominantly arranged with their long axes oriented radially, and the width of the high molecular weight aggregate corresponds to the length of two e-gp41 trimers (approximately 200 A). Using both light and electron microscopy combined with immunohistochemistry we show that HIV gp41 accumulates as an extracellular aggregate in the brains of HIV-infected patients diagnosed with dementia. We postulate that the high molecular weight aggregates of e-gp41 are responsible for HIV-associated neurological damage and dementia, consistent with known mechanisms of encephalopathy.

AIDS Dementia Complex↗