Genetic Variants of HIV-1 in Thailand

McCutchan, Francine E.; Hegerich, Patricia; Brennan, Terrence P.; Phanuphak, Praphan; Singharaj, Pricha; Jugsudee, Achara; Berman, Phillip W.; Gray, Andrew; Fowler, Arnold K.; Burke, Donald S.

doi:10.1089/aid.1992.8.1887

Cited by 236 publications

(142 citation statements)

References 16 publications

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“…Recombination plays an important role in the current AIDS epidemic. For example, many of the currently circulating primary strains of HIV-1 are actually intersubtype recombinants (32,33). Additionally, it has been shown that multidrug-resistant virus strains can be generated by recombining the genomes of two viruses, each resistant to a single drug (34).…”

Section: Reconciling the Paradox Between Single-hit Kinetics Of Virusmentioning

confidence: 99%

Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways

Dang

Chen

Unutmaz

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

113

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Cells infected with two related retroviruses can generate heterozygous virions, which are the precursors of recombinant proviruses. Although many studies have focused on the frequencies and mechanisms of retroviral recombination, little is known about the dynamics of double infection. To examine this issue, viruses generated from two HIV-1 vectors containing different markers were mixed together, and were used to infect target cells. The numbers of cells expressing none, one, or both markers were measured and were used to calculate whether double infection occurred at frequencies expected from random infection events. We found that double infection occurred significantly more frequently than predicted from random distribution; increased rates of double infection were observed in both a T cell line and primary activated CD4 ؉ T cells. In addition to direct virus infection, we also examined the nature of cell-mediated HIV-1 double infection. Increased double infection was observed in all experiments regardless of whether a cell line or primary human dendritic cells were used for capture and transmission of HIV-1. Therefore, our results indicate that HIV-1 double infection occurs more frequently than it would at random in both direct and cell-mediated HIV-1 infections. To our knowledge, this is the first direct evidence of nonrandom double infection in HIV-1. Frequent double HIV-1 infections in infected individuals would allow the generation of recombinant viruses that could then affect their pathogenesis and evolution.

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Section: Reconciling the Paradox Between Single-hit Kinetics Of Virusmentioning

confidence: 99%

Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways

Dang

Chen

Unutmaz

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

113

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“…Finally, we tested the macrophage current responses to HIV-1 primary isolates by using gp120 from the R5 Chiang Mai (CM) isolate (26) and the X4 isolate UG021 (24). Both primary isolates also activated K Ca , Cl Ϫ , and NSC currents (Table 1).…”

Section: Hiv-1 Env But Not Chemokines Activate a Nonselective Catiomentioning

confidence: 99%

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

Liu

Williams²,

McManus³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

139

130

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HIV type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry into target cells. Here we show that the HIV-1 envelope gp120 (Env) activates multiple ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. Env from both CCR5-dependent JRFL (R5) and CXCR4-dependent IIIB (X4) HIV-1 opened calcium-activated potassium (K Ca), chloride, and calcium-permeant nonselective cation channels in macrophages. These signals were mediated by CCR5 and CXCR4 because macrophages lacking CCR5 failed to respond to JRFL and an inhibitor of CXCR4 blocked ion current activation by IIIB. MIP-1␤ and SDF-1␣, chemokine ligands for CCR5 and CXCR4, respectively, also activated K Ca and Cl ؊ currents in macrophages, but nonselective cation channel activation was unique to gp120. Intracellular Ca 2؉ levels were also elevated by gp120. The patterns of activation mediated by CCR5 and CXCR4 were qualitatively similar but quantitatively distinct, as R5 Env activated the K Ca current more frequently, elicited Cl ؊ currents that were Ϸ2-fold greater in amplitude, and elevated intracellular Ca ؉2 to higher peak and steady-state levels. Env from R5 and X4 primary isolates evoked similar current responses as the corresponding prototype strains. Thus, the interaction of HIV-1 gp120 with CCR5 or CXCR4 evokes complex and distinct signaling responses in primary macrophages, and gp120-evoked signals differ from those activated by the coreceptors' chemokine ligands. Intracellular signaling responses of macrophages to HIV-1 may modulate postentry steps of infection and cell functions apart from infection.

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“…Subtype A (sub-subtypes 1 and 2) strains are highly predominant in Kenya, with one study showing 93% of all strains found in the region being subtype A or a recombinant containing subtype A (Dowling et al, 2002). In addition, CRF01_AE is one of the major strains found in Thailand and Southeast Asia (McCutchan et al, 1992;Tovanabutra et al, 2004). Subsubtype A2 was first identified from sequences originating in the Democratic Republic of Congo and Cyprus (Gao et al, 2001), and is now also found in Kenya (Visawapoka et al, 2006).…”

Section: The Global Distribution Of Hiv-1 Subtypes and Crfsmentioning

confidence: 99%

HIV Recombination and Pathogenesis – Biological and Epidemiological Implications

Saksena¹,

Lau²,

Dwyer³

et al. 2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

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Genetic Variants of HIV-1 in Thailand

Cited by 236 publications

References 16 publications

Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways

Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

HIV Recombination and Pathogenesis – Biological and Epidemiological Implications

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