Compartmentalization of Surface Envelope Glycoprotein of Human Immunodeficiency Virus Type 1 during Acute and Chronic Infection

Abstract

Human immunodeficiency virus type 1 is characterized by extensive genetic heterogeneity. Having previously demonstrated that, in the peripheral blood, the initial viral population is more homogeneous than at subsequent stages of infection, we have extended our studies to tissue samples, allowing comparisons between viral populations in peripheral blood and tissues during both the acute and chronic stages of infection. We found that homogeneity in gp120 sequences during the acute infection phase is not just restricted to the peripheral blood but also extends to other tissue compartments. However, in chronically infected individuals, heterogeneous and distinct viral populations were found in different compartments. We therefore conclude that the dominant and homogeneous viral population observed during the acute infection phase is likely to infiltrate lymphoid tissues and form the genetic bases for subsequent diversification. It is therefore likely that the compartmentalization of viral sequences observed in chronically infected patients reflects a gradual diversification of a common dominant viral variant rather than the preferential migration of distinct viral populations to different tissue compartments at the beginning of infection.

Human Immunodeficiency Virus Type 1 Genomic RNA Sequences in the Female Genital Tract and Blood: Compartmentalization and Intrapatient Recombination

“…pressure in the separate compartments (61). Another study, which examined women with a spectrum of immune states, demonstrated an association of higher CD4 ϩ cell counts and compartmentalization of HIV-1 env sequences, providing evidence that the immune response influences the development of viral genotypes in each compartment (24).…”

“…Compartmentalization has been rigorously documented in various different tissues, including the brain, blood and tissue lymphocytes, and plasma (5,27,41,59,61). HIV-1 sequence heterogeneity has also been observed in several pioneering studies of blood and genital secretions of infected women (18,24,39,45,51), but complete RNA genomes from the genital tract have not been fully characterized on a molecular level.…”

Semen-Specific Genetic Characteristics of Human Immunodeficiency Virus Type 1 env

“…Anatomic compartmentalization of these variants has been described in blood, lung, central nervous system, and genital tract (10,16,17,20,21,32,41,50,53). Male genital tract tissues (e.g., the prostate, seminal vesicles, and epididymis) serve as sites of viral replication and are likely to differ from peripheral tissues in immunological surveillance, target cell characteristics, and efficiencies of drug penetration (10,17,43).…”

“…Male genital tract tissues (e.g., the prostate, seminal vesicles, and epididymis) serve as sites of viral replication and are likely to differ from peripheral tissues in immunological surveillance, target cell characteristics, and efficiencies of drug penetration (10,17,43). Virus replicating within the male genital tract could therefore develop distinct, compartment-specific characteristics in response to these local selective pressures (10,16,17,20,21,32,41,50,53). Although genetic differences between blood-and semen-derived HIV in an individual have been documented, a seminal signature sequence remains elusive (6,10).…”

HIV-I Reverse Transcriptase Variation in Plasma and Genital Secretion of Antiretroviral-Naive Females

“…Previous studies have shown that homogeneous HIV strains will be present in blood early during the primary infection, including in women. [13][14][15][16][17][18] A possibility exists that the subtype C variants of HIV-1 mainly present in our study women may be homogeneously transmitted during male-to-female heterosexual transmission, as previously hypothesized for clade C HIV-1 variants during both female-to-male and male-to-female transmissions. 19 However, frequent heterogeneity of HIV-1 variants in blood during primary infection 19,20 has also been reported.…”