scholarly journals Monitoring Responses to Antiretroviral Treatment in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Patients by Serial Lymph Node Aspiration

1997 ◽  
Vol 175 (5) ◽  
pp. 1202-1205 ◽  
Author(s):  
Philippe Bürgisser ◽  
François Spertini ◽  
Catherine Weyrich‐Suter ◽  
Jean‐Luc Pagani ◽  
Pascal R. A. Meylan
2006 ◽  
Vol 80 (13) ◽  
pp. 6324-6332 ◽  
Author(s):  
Paul J. Peters ◽  
W. Matthew Sullivan ◽  
Maria J. Duenas-Decamp ◽  
Jayanta Bhattacharya ◽  
Chiambah Ankghuambom ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) R5 isolates that predominantly use CCR5 as a coreceptor are frequently described as macrophage tropic. Here, we compare macrophage tropism conferred by HIV-1 R5 envelopes that were derived directly by PCR from patient tissue. This approach avoids potentially selective culture protocols used in virus isolation. Envelopes were amplified (i) from blood and semen of adult patients and (ii) from plasma of pediatric patients. The phenotypes of these envelopes were compared to those conferred by an extended panel of envelopes derived from brain and lymph node that we reported previously. Our results show that R5 envelopes vary by up to 1,000-fold in their capacity to confer infection of primary macrophages. Highly macrophage-tropic envelopes were predominate in brain but were infrequent in semen, blood, and lymph node samples. We also confirmed that the presence of N283 in the C2 CD4 binding site of gp120 is associated with HIV-1 envelopes from the brain but absent from macrophage-tropic envelopes amplified from blood and semen. Finally, we compared infection of macrophages, CD4+ T cells, and peripheral blood mononuclear cells (PBMCs) conferred by macrophage-tropic and non-macrophage-tropic envelopes in the context of full-length replication competent viral clones. Non-macrophage-tropic envelopes conferred low-level infection of macrophages yet infected CD4+ T cells and PBMCs as efficiently as highly macrophage-tropic brain envelopes. The lack of macrophage tropism for the majority of the envelopes amplified from lymph node, blood, and semen is striking and contrasts with the current consensus that R5 primary isolates are generally macrophage tropic. The extensive variation in R5 tropism reported here is likely to have an important impact on pathogenesis and on the capacity of HIV-1 to transmit.


2008 ◽  
Vol 82 (12) ◽  
pp. 5807-5814 ◽  
Author(s):  
Maria José Duenas-Decamp ◽  
Paul Peters ◽  
Dennis Burton ◽  
Paul R. Clapham

ABSTRACT The human monoclonal antibody b12 recognizes a conserved epitope on gp120 that overlaps the CD4 binding site. b12 has neutralizing activity against diverse human immunodeficiency virus type 1 (HIV-1) strains. However, we recently reported that b12 sensitivity of HIV-1 envelopes amplified from patient tissues without culture varied considerably. For two subjects, there was clear modulation of b12 sensitivity, with lymph node-derived envelopes being essentially resistant while those from brain tissue were sensitive. Here, we have mapped envelope determinants of b12 resistance by constructing chimeric envelopes from resistant and sensitive envelopes derived from lymph node and brain tissue, respectively. Residues on the N-terminal flank of the CD4 binding loop conferred partial resistance. However, a potential glycosylation site at residue N386 completely modulated b12 resistance but required the presence of an arginine at residue 373. Moreover, the introduction of R373 into b12-sensitive NL4.3 and AD8 envelopes, which carry N386, also conferred b12 resistance. Molecular modeling suggests that R373 and the glycan at N386 may combine to sterically exclude the benzene ring of b12 W100 from entering a proximal pocket. In summary, we identify residues on either side of the CD4 binding loop that contribute to b12 resistance in immune tissue in vivo. Our data have relevance for the design of vaccines that aim to elicit neutralizing antibodies.


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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