Compartmentalization of the gut viral reservoir in HIV-1 infected patients.
BACKGROUND
Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1) infection. The gut associated lymphoid tissue (GALT) is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals.


RESULTS
Gut biopsies (esophagus, stomach, duodenum and colorectum) were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy) patients. HIV-1 Nef and Reverse transcriptase (RT) encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p < 0.05) and higher levels of viral genome were observed in the colorectum (p < 0.05). These differences could reflect an adaptation of HIV-1 to the various tissues.


CONCLUSIONS
Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection.
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada. vanmarle@ucalgary.ca
Guido
G
van Marle
M John
MJ
Gill
Dione
D
Kolodka
Leah
L
McManus
Tannika
T
Grant
Deirdre L
DL
Church
D000595:Amino Acid Sequence; D001483:Base Sequence; D041981:Gastrointestinal Tract / Q000473:pathology / Q000821:virology*; D015870:Gene Expression; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006716:Homosexuality; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics
D054311:nef Gene Products, Human Immunodeficiency Virus