Dr. Ling’s laboratory is interested in using simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency viruses (SHIVs) in rhesus macaques, particularly the Chinese-origin rhesus macaques (cRM), as a nonhuman primate model to study the persistence of HIV in tissues specifically the gut and central nervous system (CNS) to develop novel drug delivery and therapeutic strategies to eradicate HIV. Her team also aims to understand what controls or spreads the virus in a host with or without therapeutic intervention. Additional focuses are HIV comorbidities such as HIV/SIV and aging.
Dr. Ling’s current research is supported by NIH. She has a broad background in molecular virology, immunology, and many years of work experience and expertise in nonhuman primate models in key areas of HIV/SIV pathogenesis and cure studies.
Inside the Lab
HIV/SIV persistence in lymphoid tissues.
Her study of gut tissue reservoir revealed large intestine and mesenteric lymph nodes are major reservoirs in spontaneous controllers (SC) and animals on potent combination antiretroviral therapy (cART). The lab further explores dynamic changes of gut microbiota and immune activation during long-term cART that may contribute to SIV persistence. Working with collaborators, novel strategies of delivery of potent drugs to the gut and mesenteric lymph nodes are also in development.
Viral reservoirs in the CNS.
Persistence of HIV in the CNS is another obstacle to a HIV cure. Current studies include the role of myeloid cells as cellular reservoirs and the potential source of viral rebound in the CNS, as well as the use of novel technologies such as CRISPR-Cas 9 editing system to test the potential for eradication of the virus in infected cells.
Host responses in immune protection and correlation.
Previous studies showed that SIV/cRM model is featured with a relatively high frequency of SC similar to HIV-infected long term non-progressors. Her team continuously work to understand the mechanism(s) of immune correlates with this slower progression with or without therapy, particularly the role of NK cells during early infection, for novel therapeutics.
HIV/SIV and aging.
HIV infection may play a role in accentuated and/or accelerated aging such as age-associated neurocognitive dysfunction. The team uses the SIV-infected rhesus macaques on cART to determine factors such as SIV and antiretroviral drugs themselves contribute to sustained neuroinflammation, cellular senescence and senescence-associated secretory phenotype (SASP) in brain aging in the nonhuman primate model of HIV infection on cART.
Main Technologies and Methods Used
Flow cytometry and cell sorting
In situ hybridization, RNAscope
Immunofluorescence, confocal microscopy
CRISPR and other gene editing technologies in vivo application
Quantitative PCR, qRT-PCR, ddPCR, deep sequencing, and transcriptomics