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Non-syncytium-inducing HIV type 1 isolated from infected individuals replicates in MT-2 cells
S E Forte1, K S Byron, J L Sullivan
1Department of Pediatrics, University of Massachusetts Medical School, Worcester 01605.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) isolates from six infected individuals less then 4 years of age were phenotyped for their syncytium-inducing (SI) ability in MT-2 cells. Three viral isolates that induced syncytia were detected. One SI isolate was from an individual who was in disease stage P2A,B,C and two SI isolates were recovered sequentially from another individual who switched from disease stage P1B to P2F. Non-syncytium-inducing (NSI) isolates were detected in two individuals who were in stage P1B of disease, and in a third individual who was in stage P2A of disease. Three sequential isolates obtained over a 2-year period from a fourth individual who progressed from disease stage P1B to P2A,B,C and subsequently died of AIDS-related disease were also found to have the NSI phenotype. To test whether NSI isolates can replicate in the absence of syncytium formation, we analyzed NSI-infected MT-2 cells for production of viral p24 antigen and expression of viral RNA by in situ hybridization. By day 12 postinfection, 6 of 7 NSI viral isolates produced 7- to 36-fold increases in p24 antigen compared to day 6, and expressed viral RNA in 13-20% of cells. A single NSI isolate that did not replicate in MT-2 cells was obtained from an individual who was asymptomatic (stage P1B). The individual rapidly progressed to symptomatic stage P2F and two sequential SI viruses were isolated. These SI isolates replicated in MT-2 cells and induced cytopathic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Syncytium-inducing (SI) and non-syncytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) isolates were identified in children. Some NSI isolates replicated in MT-2 cells, while SI isolates showed cytopathic effects.
Area of Science:
- Virology
- Immunology
- Pediatric infectious diseases
Background:
- Human immunodeficiency virus type 1 (HIV-1) exhibits diverse phenotypes.
- Syncytium-inducing (SI) and non-syncytium-inducing (NSI) phenotypes are associated with disease progression.
Purpose of the Study:
- To phenotype HIV-1 isolates from children for syncytium-inducing ability.
- To assess the replication capacity of NSI isolates in MT-2 cells.
Main Methods:
- Phenotyping of HIV-1 isolates from children using MT-2 cell syncytium-induction assay.
- Analysis of viral p24 antigen production and viral RNA expression in NSI-infected MT-2 cells.
Main Results:
- Three SI HIV-1 isolates were detected in individuals with advanced disease.
- Six of seven NSI isolates replicated in MT-2 cells, showing increased p24 antigen and viral RNA expression.
- One NSI isolate from an asymptomatic individual failed to replicate initially but was followed by SI isolates after disease progression.
Conclusions:
- HIV-1 isolates from children can exhibit both SI and NSI phenotypes.
- NSI isolates demonstrate replication capacity in vitro, suggesting potential for viral activity.
- The emergence of SI isolates may correlate with disease progression in pediatric HIV-1 infection.