PMID- 10417737
OWN - NLM
STAT- MEDLINE
DCOM- 19990922
LR  - 20191103
IS  - 1081-650X (Print)
IS  - 1081-650X (Linking)
VI  - 111
IP  - 4
DP  - 1999 Jul-Aug
TI  - Genetic determinants of HIV-1 infection and its manifestations.
PG  - 299-307
AB  - The human immunodeficiency virus type 1 (HIV-1), which has become pandemic within 
      a single generation, has encountered an immune system in which genetically 
      encoded elements have evolved gradually under different environmental pressures 
      in diverse populations. Important heritable differences in genes that alter 
      susceptibility to HIV-1 infection or the rate of deterioration of immunity, or 
      both, have been discovered in cohorts carefully defined for intensity of exposure 
      to the virus, viral subtype characteristics, and onset and course of infection. 
      For the highly polymorphic human leukocyte antigen (HLA) antigen processing and 
      presenting system, the principle that small contributions of multiple interactive 
      HLA marker combinations (primarily in the class I pathway) significantly modulate 
      the course of HIV-1 infection has now been confirmed in several independently 
      evaluated groups of patients. Variants of HLA genes probably also play some role 
      in the acquisition of infection by the various routes of transmission. Genes for 
      an elaborate set of circulating chemokine molecules and their cell-surface 
      receptors clearly regulate cell attachment and penetration of HIV. Certain 
      allelic forms of one, the CCR5 gene, alter susceptibility to infection and the 
      rate of progression of disease; in the homozygous state, a deleted form (Delta32 
      CCR5) strongly protects against infection, and in infected heterozygotes, it 
      slows the disease process somewhat. Mutants in genes of other chemokine system 
      components further differentiate the response to infection, and frequencies of 
      these forms vary between and within races. Work relating additional genetic 
      markers to HIV infection or disease is at earlier stages. Dissecting the effects 
      of multiple variants in complex gene systems will clearly require organized 
      comprehensive approaches in considerably larger populations than have typically 
      been assembled.
FAU - Kaslow, R A
AU  - Kaslow RA
AD  - Department of Epidemiology, University of Alabama at Birmingham, 35294-0022, USA.
FAU - McNicholl, J M
AU  - McNicholl JM
LA  - eng
GR  - R01-AI41951/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Proc Assoc Am Physicians
JT  - Proceedings of the Association of American Physicians
JID - 9514310
RN  - 0 (CD4 Antigens)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Alleles
MH  - Antigen Presentation/genetics
MH  - CD4 Antigens/genetics
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/genetics
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - HIV Infections/epidemiology/*genetics
MH  - HIV-1/*physiology
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Life Tables
MH  - Male
MH  - Receptors, Chemokine/genetics
MH  - Structure-Activity Relationship
MH  - T-Lymphocytes, Cytotoxic/immunology
RF  - 62
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
AID - paa99238 [pii]
AID - 10.1046/j.1525-1381.1999.99238.x [doi]
PST - ppublish
SO  - Proc Assoc Am Physicians. 1999 Jul-Aug;111(4):299-307. doi: 
      10.1046/j.1525-1381.1999.99238.x.