scholarly journals The clinical significance of human immunodeficiency virus type 1- associated paraproteins

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2471-2475 ◽  
Author(s):  
VL Ng ◽  
KH Chen ◽  
KM Hwang ◽  
H Khayam-Bashi ◽  
MS McGrath

Abstract We observed and characterized paraproteins present in the serum of seven human immunodeficiency virus type 1 (HIV-1)-infected individuals. Immunoglobulin (Ig) subclass typing performed on these paraproteins identified five as IgG1 kappa, one as an IgG3 lambda, and one as an IgA lambda. The IgG1 kappa paraproteins, purified by high-pressure liquid chromatography, contained the majority of anti-HIV-1 antibody reactivity present in the five serum specimens (ranging from 1:5,000 to 1:500,000) as demonstrated by immunoblot. All five IgG1 paraproteins had at least two light chain species as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the antibodies were reactive with multiple HIV-1 viral antigens. In contrast, the electrophoretically purified IgG3 lambda and IgA lambda paraproteins did not react with HIV-1 antigens and only one light chain species was detected by SDS-PAGE. The subsequent clinical evaluation of these patients following the initial observation of paraproteinemias failed to correlate the presence of paraproteins with the development of lymphoma over a 2 to 3 year period. These data support the hypothesis that IgG1 paraproteins present in the sera of HIV-1 infected individuals reflect a normal albeit exuberant polyclonal immune response to HIV-1 viral antigens. In contrast, the clinical significance of an IgG3 lambda or an IgA lambda paraprotein is unclear at present.

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2471-2475
Author(s):  
VL Ng ◽  
KH Chen ◽  
KM Hwang ◽  
H Khayam-Bashi ◽  
MS McGrath

We observed and characterized paraproteins present in the serum of seven human immunodeficiency virus type 1 (HIV-1)-infected individuals. Immunoglobulin (Ig) subclass typing performed on these paraproteins identified five as IgG1 kappa, one as an IgG3 lambda, and one as an IgA lambda. The IgG1 kappa paraproteins, purified by high-pressure liquid chromatography, contained the majority of anti-HIV-1 antibody reactivity present in the five serum specimens (ranging from 1:5,000 to 1:500,000) as demonstrated by immunoblot. All five IgG1 paraproteins had at least two light chain species as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the antibodies were reactive with multiple HIV-1 viral antigens. In contrast, the electrophoretically purified IgG3 lambda and IgA lambda paraproteins did not react with HIV-1 antigens and only one light chain species was detected by SDS-PAGE. The subsequent clinical evaluation of these patients following the initial observation of paraproteinemias failed to correlate the presence of paraproteins with the development of lymphoma over a 2 to 3 year period. These data support the hypothesis that IgG1 paraproteins present in the sera of HIV-1 infected individuals reflect a normal albeit exuberant polyclonal immune response to HIV-1 viral antigens. In contrast, the clinical significance of an IgG3 lambda or an IgA lambda paraprotein is unclear at present.


1991 ◽  
Vol 32 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Luigi M.E. Grimaldi ◽  
Antonella Castagna ◽  
Davide Maimone ◽  
Gian Vito Martino ◽  
Alberto Dolci ◽  
...  

2015 ◽  
Vol 89 (7) ◽  
pp. 3497-3511 ◽  
Author(s):  
Kallesh Danappa Jayappa ◽  
Zhujun Ao ◽  
Xiaoxia Wang ◽  
Andrew J. Mouland ◽  
Sudhanshu Shekhar ◽  
...  

ABSTRACTIn this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Gluedin early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs52GQVD and250VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1INQ53A/Q252A) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1INQ53A/Q252Amutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1.IMPORTANCEHost cellular DYNLL1, DYNLT1, and p150Gluedproteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral replication steps.


1994 ◽  
Vol 70 (6) ◽  
Author(s):  
Marisa Márcia Mussi-Pinhata ◽  
Maria Célia C. Ferez ◽  
Dimas T. Covas ◽  
Geraldo Duarte ◽  
Márcia L. Isaac ◽  
...  

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