Neuropsychological studies of asymptomatic Human Immunodeficiency Virus-Type-1 infected individuals

1995 ◽  
Vol 1 (3) ◽  
pp. 304-315 ◽  
Author(s):  
Desirée A. White ◽  
Robert K. Heaton ◽  
Andreas U. Monsch ◽  

AbstractThe current review was conducted to address the ongoing debate regarding the presence or absence of neuropsychological impairment in asymptomatic HIV-Type 1 (HIV-1) seropositive individuals. Results were summarized from 57 studies that compared the performances of seropositive asymptomatic and seronegative individuals. Overall, the differences observed between median rates of impairment for asymptomatic (35%) and seronegative (12%) groups provided the clearest indication of deficits in asymptomatics. In addition, five variables were examined as possible contributors to inconsistencies found in the literature: mode of infection, test battery type, test battery size, sample size, and method of data analysis. Of these variables, only mode of infection and test battery size appeared to substantially influence the outcome of the studies reviewed with regard to identifying neuropsychological impairment in asymptomatics. (JINS, 1995, I, 304–315.)

2007 ◽  
Vol 81 (22) ◽  
pp. 12210-12217 ◽  
Author(s):  
Greg Brennan ◽  
Yury Kozyrev ◽  
Toshiaki Kodama ◽  
Shiu-Lok Hu

ABSTRACT The TRIM5 family of proteins contains a RING domain, one or two B boxes, and a coiled-coil domain. The TRIM5α isoform also encodes a C-terminal B30.2(SPRY) domain, differences within which define the breadth and potency of TRIM5α-mediated retroviral restriction. Because Macaca nemestrina animals are susceptible to some human immunodeficiency virus (HIV) isolates, we sought to determine if differences exist in the TRIM5 gene and transcripts of these animals. We identified a two-nucleotide deletion (Δ2) in the transcript at the 5′ terminus of exon 7 in all M. nemestrina TRIM5 cDNA clones examined. This frameshift results in a truncated protein of 300 amino acids lacking the B30.2(SPRY) domain, which we have named TRIM5θ. This deletion is likely due to a single nucleotide polymorphism that alters the 3′ splice site between intron 6 and exon 7. In some clones, a deletion of the entire 27-nucleotide exon 7 (Δexon7) resulted in the restoration of the TRIM5 open reading frame and the generation of another novel isoform, TRIM5η. There are 18 amino acid differences between M. nemestrina TRIM5η and Macaca mulatta TRIM5α, some of which are at or near locations previously shown to affect the breadth and potency of TRIM5α-mediated restriction. Infectivity assays performed on permissive CrFK cells stably transduced with TRIM5η or TRIM5θ show that these isoforms are incapable of restricting either HIV type 1 (HIV-1) or simian immunodeficiency virus infection. The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo.


2001 ◽  
Vol 75 (6) ◽  
pp. 3038-3042 ◽  
Author(s):  
Markus Hildinger ◽  
Matthias T. Dittmar ◽  
Patricia Schult-Dietrich ◽  
Boris Fehse ◽  
Barbara S. Schnierle ◽  
...  

ABSTRACT Peptides derived from the heptad repeats of human immunodeficiency virus (HIV) gp41 envelope glycoprotein, such as T20, can efficiently inhibit HIV type 1 (HIV-1) entry. In this study, replication of HIV-1 was inhibited more than 100-fold in a T-helper cell line transduced with a retrovirus vector expressing membrane-anchored T20 on the cell surface. Inhibition was independent of coreceptor usage.


Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2337-2346 ◽  
Author(s):  
MV Ragni ◽  
DA Amato ◽  
ML LoFaro ◽  
V DeGruttola ◽  
C Van Der Horst ◽  
...  

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.


2000 ◽  
Vol 181 (2) ◽  
pp. 746-749 ◽  
Author(s):  
Melanie C. M. Murray ◽  
Joanne E. Embree ◽  
Sue G. Ramdahin ◽  
Aggrey O. Anzala ◽  
Simon Njenga ◽  
...  

1992 ◽  
Vol 165 (6) ◽  
pp. 1012-1019 ◽  
Author(s):  
Mario Clerici ◽  
Janis V. Giorgi ◽  
Chen-Cheng Chou ◽  
Vaheideh K. Gudeman ◽  
Jerome A. Zack ◽  
...  

2002 ◽  
Vol 185 (10) ◽  
pp. 1409-1416 ◽  
Author(s):  
Akihiko Saitoh ◽  
Karen Hsia ◽  
Terence Fenton ◽  
Christine A. Powell ◽  
Cindy Christopherson ◽  
...  

2001 ◽  
Vol 75 (13) ◽  
pp. 5812-5822 ◽  
Author(s):  
Brian R. Lane ◽  
Robert M. Strieter ◽  
Michael J. Coffey ◽  
David M. Markovitz

ABSTRACT We examined the early effects of infection by CCR5-using (R5 human immunodeficiency virus [HIV]) and CXCR4-using (X4 HIV) strains of HIV type 1 (HIV-1) on chemokine production by primary human monocyte-derived macrophages (MDM). While R5 HIV, but not X4 HIV, replicated in MDM, we found that the production of the C-X-C chemokine growth-regulated oncogene alpha (GRO-α) was markedly stimulated by X4 HIV and, to a much lesser extent, by R5 HIV. HIV-1 gp120 engagement of CXCR4 initiated the stimulation of GRO-α production, an effect blocked by antibodies to CXCR4. GRO-α then fed back and stimulated HIV-1 replication in both MDM and lymphocytes, and antibodies that neutralize GRO-α or CXCR2 (the receptor for GRO-α) markedly reduced viral replication in MDM and peripheral blood mononuclear cells. Therefore, activation of MDM by HIV-1 gp120 engagement of CXCR4 initiates an autocrine-paracrine loop that may be important in disease progression after the emergence of X4 HIV.


2010 ◽  
Vol 84 (8) ◽  
pp. 3935-3948 ◽  
Author(s):  
Bettina Stolp ◽  
Libin Abraham ◽  
Jochen M. Rudolph ◽  
Oliver T. Fackler

ABSTRACT Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo. We recently described for HIV type 1SF2 (HIV-1SF2) the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin and thus blocks the chemokine-mediated actin remodeling required for cell motility. However, the efficiency of PAK2 association is highly variable among Nef proteins from different lentiviruses, prompting us to evaluate the conservation of this actin-remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17 HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine-induced actin remodeling as well as inactivation of cofilin are strongly conserved activities of lentiviral Nef proteins. Of note, even for Nef variants that display only marginal PAK2 association in vitro, these activities require the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2. Thus, reduced in vitro affinity to PAK2 does not indicate limited functionality of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin remodeling as a highly conserved function of lentiviral Nef proteins, supporting the notion that PAK2 association may be critical for Nef's activity in vivo.


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