This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ritola, K.
Right arrow Articles by Swanstrom, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ritola, K.
Right arrow Articles by Swanstrom, R.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10830-10834, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10830-10834.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Increased Human Immunodeficiency Virus Type 1 (HIV-1) env Compartmentalization in the Presence of HIV-1-Associated Dementia

Kimberly Ritola,1,2 Kevin Robertson,3,6 Susan A. Fiscus,1,4 Colin Hall,3,6 and Ronald Swanstrom1,4,5*

UNC Center for AIDS Research,1 Curriculum in Genetics and Molecular Biology,2 Departments of Medicine,3 Microbiology and Immunology,4 Biochemistry and Biophysics,5 Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina6

Received 29 January 2005/ Accepted 26 April 2005


arrow
ABSTRACT
 
The human immunodeficiency virus type 1 (HIV-1) surface Env protein has been implicated in the development of HIV-1-associated dementia (HAD). HIV-1 env diversity was analyzed by heteroduplex tracking assay in 27 infected subjects with various neurological statuses. env compartmentalization between the blood and cerebral spinal fluid (CSF) was apparent with all neurological categories. However, in subjects with HAD, significantly more CSF virus was represented by CNS-unique env variants. Variants specialized for replication in the CNS may play a larger role in the development of HAD. Alternatively, HAD may be associated with a more pronounced state of immunosuppression that permits more extensive replication and independent evolution within the CNS compartment.


arrow
TEXT
 
Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) develops within a subset of HIV-1-infected subjects (16, 19, 30). HAD incidence has decreased with the advent of highly active antiretroviral therapy; however, HAD prevalence has increased with longevity (16, 19, 30). HAD is characterized by severe cognitive dysfunction and is generally combined with motor decline. HIV-1-infected patients without dementia frequently have impaired neurological performance in comparison to matched controls. This condition has been termed minor cognitive motor disorder (MCMD) (22, 24). The relationship between MCMD and HAD is unclear.

HIV-1 is present in the central nervous system (CNS) during all stages of disease (4, 10, 11). Essentially identical viral populations are detected in the blood plasma (BP) and cerebral spinal fluid (CSF) within a month of infection (29). The presence of distinct neuropathogenic virus in the CNS is one possible cause of MCMD and HAD. Distinct variants of HIV-1 can replicate in the CNS (1, 3, 7, 8, 12, 14, 15, 20, 21, 35-37, 39), and HIV-1 env variants have been implicated in HAD pathology (23). In this study, env compartmentalization of the blood and CSF was compared among subjects with HAD, MCMD, or no neurological deficits. Viral diversities were measured within the V1/V2 and V3 domains of env by heteroduplex tracking assay (HTA) (5, 6).

Studies of env diversity have predominantly employed cloning to detect major differences between virus in the periphery and virus in the CNS (1-3, 9, 14, 15, 17, 20, 21, 27, 32, 33, 37, 38, 40). HTA differs notably from cloning in that a large number of viral genotypes can be sampled at the same time. The quality of viral population sampling can easily be verified by reproducing the complex HTA banding patterns. All reverse transcriptase (RT)-PCRs and HTA reactions were performed in duplicate to validate the quality of sampling in our analyses. Examples of the reproducibility of sampling are shown in panels A of Fig. 1 and 2 and in Table 1.



View larger version (78K):
[in this window]
[in a new window]
  		FIG. 1. V1/V2 HTA of blood plasma and CSF viral variants. (A) V1/V2 HTA showing reproducibility of duplicate samples. (B) Subjects with identical variants present in the same relative abundance. (C) Subjects with identical variants present in differing relative abundances. (D) Subjects with unique variants detected in the blood plasma. (E) Subjects with unique variants detected in the CSF. (F) Subjects with unique variants detected in both the blood plasma and CSF. Dementia status is indicated as 0 (no neurological deficits), MCMD, or HAD. All subjects were diagnosed with AIDS except those indicated by Sx (symptomatic) and ASx (asymptomatic). Subject numbers are indicated at the tops of the lanes. Asterisks indicate the single-stranded probe. Circles indicate variants detected in only one compartment. B, blood plasma; C, CSF.



View larger version (54K):
[in this window]
[in a new window]
  		FIG. 2. V3 HTA of blood plasma and CSF viral variants. (A) V3 HTA showing reproducibility of duplicate samples. (B) Subjects with identical variants present in the same relative abundance. (C) Subjects with identical variants present in differing relative abundances. (D) Subjects with unique variants detected in the blood plasma. (E) Subjects with unique variants detected in the CSF. (F) Subjects with unique variants detected in both the blood plasma and CSF. Dementia status is indicated as 0 (no neurological deficits), MCMD, or HAD. All subjects were diagnosed with AIDS except those indicated by Sx (symptomatic) and ASx (asymptomatic). Arrows indicate the probe homoduplex. Circles identify variants detected in only one compartment. Open circles indicate variants inferred to use CXCR4 by V3 sequence analysis. Subject numbers are indicated at the tops of the lanes. B, blood plasma; C, CSF. (G) V3 peptide sequence analysis of subjects with CXCR4-using variants. X4-like changes are indicated in bold. Sequences were shared between the blood plasma and CSF.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Subject characteristicsa

env diversity in 27 HIV-1-infected subjects was assessed. Subjects were not receiving therapy at the time that blood and CSF were collected unless otherwise noted. Subject characteristics are described in Table 1. Viral variants from matched BP and CSF samples were amplified by RT-PCR with primers for the V1/V2 or V3 region of env (13, 18). Resulting amplification products were annealed to a strand-specific, radioactive DNA probe representing the region amplified (13, 18). Heteroduplexes were resolved by electrophoresis in a nondenaturing polyacrylamide gel followed by exposure to X-ray film.

Distinct viral genotypes are resolved when sequence differences (insertions, deletions, and clustered mismatches) between the probe and target sequence alter the conformation of the DNA duplex. Various heteroduplex conformations migrate differently through the gel, resulting in their resolution as distinct bands in the gel. A sequence difference (without length differences) of 1 to 2% between the target and the probe is typically sufficient to see a shift (5). Resolution between variants with small sequence differences can be enhanced by the use of heterologous probes containing scattered sequence and length differences relative to the target (6, 13, 18, 26). The HTA is useful in identifying and quantitating both major and minor variants (28). The relative abundance of each variant was analyzed by using phosphorimager technology. In this manner, the viral populations in these compartments were compared.

Compartmentalization between the BP and CSF was clearly evident in the V1/V2 region for the majority of subjects (Fig. 1). A sequence was considered compartmentalized if it was detected in only one compartment (unique) or if shared variants were present in differing relative abundances (enriched) between compartments. Subjects fell into one of the following five compartmentalization categories: (i) no difference in either the variants present or their relative abundances in each compartment (6/22 subjects) (Fig. 1B), (ii) no difference in the identities of variants but shared variants enriched in either BP or CSF (2/22 subjects) (Fig. 1C), (iii) unique variants detected only in the BP (1/22 subjects) (Fig. 1D), (iv) unique variants detected only in the CSF (7/22 subjects) (Fig. 1E), and (v) unique variants detected in both compartments (6/22 subjects) (Fig. 1F). Unique CSF variants, presumably from CNS sources, were detected in 13/22 subjects (Fig. 1E and F).

The V3 region was less diverse and less compartmentalized than the V1/V2 region (Fig. 2). The same five categories of compartmentalization seen in the V1/V2 region were repeated in the V3 region. However, the majority of subjects (12/24) showed no difference in the identity or relative abundance of variants found in the BP and CSF (Fig. 2B). Identical variants were present but enriched in one compartment in 3/24 subjects (Fig. 2C). Unique variants were detected in the BP of 3/24 subjects (Fig. 2D) and in the CSF of 5/24 subjects (Fig. 2E). One subject had a detectable unique variant in each compartment (Fig. 2F). V3 sequence analysis of the majority of variants from 22/24 subjects showed almost exclusive use of the CCR5 coreceptor. An X4 variant was shared between the BP and CSF of two subjects, MCMD subject 301 and HAD subject 2778 (Fig. 2C and E). While it is clear that CXCR4 usage is not required for the development of HAD, further work is needed to assess whether the presence of CXCR4-using variants in the CNS affects progression to HAD.

Shannon entropy [{Sigma}p(i)logp(i)] (31) was calculated to assess overall diversity in V1/V2 and V3. The relative abundance of each band [p(i)] and the number of bands (i [i = 1, ... n, where n is the number of bands]) within a compartment determines the level of entropy. Subjects with many bands with an equal relative abundance would have a high entropy value. A subject with a single variant would have an entropy value of 0. Entropies were not different between compartments within a neurological group or within the same compartment between neurological groups. However, in subjects with HAD, a significantly greater percent of the CSF viral RNA represented CNS-unique variants (P = 0.01, Wilcoxon rank sum test). CNS-unique variants contributed 40 to 96% (median, 62%) of the CSF virus in subjects with HAD, as opposed to 5 to 43% (median, 25%) in subjects without HAD (Table 1). The inability to detect CSF-unique variants in the blood was not the result of bias due to poor sampling; blood RT-PCR amplifications contained a greater number of viral RNA templates than their matched CSF reactions in all subjects except four (one with HAD, two with MCMD, and one with no neurological dysfunction).

Subjects with AIDS had significantly lower CD4 T-cell counts (P = 0.001, Wilcoxon rank sum test). Subjects with HAD had significantly lower CD4 T-cell counts than subjects without dementia (P = 0.01, Wilcoxon rank sum test). Among subjects with AIDS, HAD subjects had significantly lower CD4 counts (P = 0.045, Wilcoxon rank sum test). The difference in CD4 T-cell counts between subjects with MCMD and subjects with no neurological symptoms was not significant (P = 0.7, Wilcoxon rank sum test). Subjects with HAD did not have significantly higher CSF viral loads (P = 0.07, Wilcoxon rank sum test) or BP viral loads (P = 0.16, Wilcoxon rank sum test) than subjects without dementia.

In summary, compartmentalized env variants, either unique or enriched, were readily detected in the CSF. However, the appearance of compartmentalized variants in either the V1/V2 or V3 region did not correlate with neurological disease status. Furthermore, overall diversity was not correlated with neurological disease status. However, subjects with HAD had a greater percentage of CSF virus representing CNS-unique viral variants than subjects without HAD. Previous work suggests that as neurological disease progresses, the viral load source in the CSF becomes more CNS source dependent (7, 8, 34). More specifically, we found that CNS-unique variants, not variants also detected in the periphery, are significantly increased in the CSF during HAD. Increased representation of CNS variants in the CSF may be due to decreased movement of CD4 T-cells between the periphery and CSF, as proposed by Ellis et al. and Price et al. (8, 25). Subjects with HAD that were in our cohort had significantly lower CD4 counts. Pronounced immunological failure may also lead to increased replication and, thus, outgrowth of CNS-unique variants that are then shed into the CSF. It is unclear whether increased replication of CNS-unique variants and/or a novel phenotype of those variants is involved in the development of HAD.


arrow
ACKNOWLEDGMENTS
 
This study was supported by National Institutes of Health grants R01-MH62690, R01-MH067751, and GCRC-RR00046 and the University of North Carolina Center for AIDS Research (P30-AI50410). K.R. was supported in part by National Institutes of Health training grant T32-AI007419.

We thank Laura Lapkauskaite (Department of Biostatistics, University of North Carolina—Chapel Hill) for her assistance with the statistical analysis.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: University of North Carolina at Chapel Hill, UNC Center for AIDS Research, Lineberger Building, Chapel Hill, NC 27599-7295. Phone: (919) 966-5710. Fax: (919) 966-8212. E-mail: risunc{at}med.unc.edu. Back


arrow
REFERENCES
 
    1
  1. Babas, T., D. Munoz, J. L. Mankowski, P. M. Tarwater, J. E. Clements, and M. C. Zink. 2003. Role of microglial cells in selective replication of simian immunodeficiency virus genotypes in the brain. J. Virol. 77:208-216.
    2. 2
  2. Chang, J., R. Jozwiak, B. Wang, T. Ng, Y. C. Ge, W. Bolton, D. E. Dwyer, C. Randle, R. Osborn, A. L. Cunningham, and N. K. Saksena. 1998. Unique HIV type 1 V3 region sequences derived from six different regions of brain: region-specific evolution within host-determined quasispecies. AIDS Res. Hum. Retrovir. 14:25-30.[Medline]
    3. 3
  3. Chen, H., C. Wood, and C. K. Petito. 2000. Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis. J. Neurovirol. 6:498-506.[Medline]
    4. 4
  4. Davis, L. E., B. L. Hjelle, V. E. Miller, D. L. Palmer, A. L. Llewellyn, T. L. Merlin, S. A. Young, R. G. Mills, W. Wachsman, and C. A. Wiley. 1992. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 42:1736-1739.[Abstract/Free Full Text]
    5. 5
  5. Delwart, E. L., and C. J. Gordon. 1997. Tracking changes in HIV-1 envelope quasispecies using DNA heteroduplex analysis. Methods 12:348-354.[CrossRef][Medline]
    6. 6
  6. Delwart, E. L., E. G. Shpaer, J. Louwagie, F. E. McCutchan, M. Grez, H. Rubsamen-Waigmann, and J. I. Mullins. 1993. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science 262:1257-1261.[Abstract/Free Full Text]
    7. 7
  7. Eggers, C., K. Hertogs, H. J. Sturenburg, J. van Lunzen, and H. J. Stellbrink. 2003. Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS 17:1897-1906.[CrossRef][Medline]
    8. 8
  8. Ellis, R. J., A. C. Gamst, E. Capparelli, S. A. Spector, K. Hsia, T. Wolfson, I. Abramson, I. Grant, and J. A. McCutchan. 2000. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54:927-936.[Abstract/Free Full Text]
    9. 9
  9. Epstein, L. G., C. Kuiken, B. M. Blumberg, S. Hartman, L. R. Sharer, M. Clement, and J. Goudsmit. 1991. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology 180:583-590.[CrossRef][Medline]
    10. 10
  10. Gisslen, M., L. Hagberg, D. Fuchs, G. Norkrans, and B. Svennerholm. 1998. Cerebrospinal fluid viral load in HIV-1-infected patients without antiretroviral treatment: a longitudinal study. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 17:291-295.[Medline]
    11. 11
  11. Goudsmit, J., F. de Wolf, D. A. Paul, L. G. Epstein, J. M. Lange, W. J. Krone, H. Speelman, E. C. Wolters, J. Van der Noordaa, J. M. Oleske, et al. 1986. Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet ii:177-180.
    12. 12
  12. Haas, D. W., B. W. Johnson, P. Spearman, S. Raffanti, J. Nicotera, D. Schmidt, T. Hulgan, R. Shepard, and S. A. Fiscus. 2003. Two phases of HIV RNA decay in CSF during initial days of multidrug therapy. Neurology 61:1391-1396.[Abstract/Free Full Text]
    13. 13
  13. Kitrinos, K. M., N. G. Hoffman, J. A. Nelson, and R. Swanstrom. 2003. Turnover of env variable region 1 and 2 genotypes in subjects with late-stage human immunodeficiency virus type 1 infection. J. Virol. 77:6811-6822.[Abstract/Free Full Text]
    14. 14
  14. Korber, B. T., K. J. Kunstman, B. K. Patterson, M. Furtado, M. M. McEvilly, R. Levy, and S. M. Wolinsky. 1994. Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J. Virol. 68:7467-7481.[Abstract/Free Full Text]
    15. 15
  15. Kuiken, C. L., J. Goudsmit, G. F. Weiller, J. S. Armstrong, S. Hartman, P. Portegies, J. Dekker, and M. Cornelissen. 1995. Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex. J. Gen. Virol. 76:175-180.[Abstract/Free Full Text]
    16. 16
  16. McArthur, J. C., N. Haughey, S. Gartner, K. Conant, C. Pardo, A. Nath, and N. Sacktor. 2003. Human immunodeficiency virus-associated dementia: an evolving disease. J. Neurovirol. 9:205-221.[Medline]
    17. 17
  17. Morris, A., M. Marsden, K. Halcrow, E. S. Hughes, R. P. Brettle, J. E. Bell, and P. Simmonds. 1999. Mosaic structure of the human immunodeficiency virus type 1 genome infecting lymphoid cells and the brain: evidence for frequent in vivo recombination events in the evolution of regional populations. J. Virol. 73:8720-8731.[Abstract/Free Full Text]
    18. 18
  18. Nelson, J. A. E., S. A. Fiscus, and R. Swanstrom. 1997. Evolutionary variants of the human immunodeficiency virus type 1 V3 region characterized by using a heteroduplex tracking assay. J. Virol. 71:8750-8758.[Abstract]
    19. 19
  19. Neuenburg, J. K., H. R. Brodt, B. G. Herndier, M. Bickel, P. Bacchetti, R. W. Price, R. M. Grant, and W. Schlote. 2002. HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 31:171-177.
    20. 20
  20. Pang, S., H. V. Vinters, T. Akashi, W. A. O'Brien, and I. S. Chen. 1991. HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J. Acquir. Immune Defic. Syndr. 4:1082-1092.
    21. 21
  21. Power, C., J. C. McArthur, R. T. Johnson, D. E. Griffin, J. D. Glass, S. Perryman, and B. Chesebro. 1994. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J. Virol. 68:4643-4649.[Abstract/Free Full Text]
    22. 22
  22. Power, C., J. C. McArthur, A. Nath, K. Wehrly, M. Mayne, J. Nishio, T. Langelier, R. T. Johnson, and B. Chesebro. 1998. Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients. J. Virol. 72:9045-9053.[Abstract/Free Full Text]
    23. 23
  23. Power, C., K. Zhang, and G. van Marle. 2004. Comparative neurovirulence in lentiviral infections: The roles of viral molecular diversity and select proteases. J. Neurovirol. 10(Suppl. 1):113-117.
    24. 24
  24. Price, R. W., B. Brew, J. Sidtis, M. Rosenblum, A. C. Scheck, and P. Cleary. 1988. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586-592.[Abstract/Free Full Text]
    25. 25
  25. Price, R. W., E. E. Paxinos, R. M. Grant, B. Drews, A. Nilsson, R. Hoh, N. S. Hellmann, C. J. Petropoulos, and S. G. Deeks. 2001. Cerebrospinal fluid response to structured treatment interruption after virological failure. AIDS 15:1251-1259.[CrossRef][Medline]
    26. 26
  26. Quinones-Mateu, M. E., S. C. Ball, A. J. Marozsan, V. S. Torre, J. L. Albright, G. Vanham, G. van Der Groen, R. L. Colebunders, and E. J. Arts. 2000. A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J. Virol. 74:9222-9233.[Abstract/Free Full Text]
    27. 27
  27. Reddy, R. T., C. L. Achim, D. A. Sirko, S. Tehranchi, F. G. Kraus, F. Wong-Staal, and C. A. Wiley. 1996. Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis. AIDS Res. Hum. Retrovir. 12:477-482.[Medline]
    28. 28
  28. Resch, W., N. Parkin, E. L. Stuelke, T. Watkins, and R. Swanstrom. 2001. A multiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics. Proc. Natl. Acad. Sci. USA 98:176-181.[Abstract/Free Full Text]
    29. 29
  29. Ritola, K., C. D. Pilcher, S. A. Fiscus, N. G. Hoffman, J. A. Nelson, K. M. Kitrinos, C. B. Hicks, J. J. Eron, Jr., and R. Swanstrom. 2004. Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1. J. Virol. 78:11208-11218.[Abstract/Free Full Text]
    30. 30
  30. Sacktor, N., M. P. McDermott, K. Marder, G. Schifitto, O. A. Selnes, J. C. McArthur, Y. Stern, S. Albert, D. Palumbo, K. Kieburtz, J. A. De Marcaida, B. Cohen, and L. Epstein. 2002. HIV-associated cognitive impairment before and after the advent of combination therapy. J. Neurovirol. 8:136-142.[Medline]
    31. 31
  31. Shannon, C. E., and W. Weaver. 1949. The mathematical theory of communication. University of Illinois Press, Champaign, Ill.
    32. 32
  32. Shapshak, P., D. M. Segal, K. A. Crandall, R. K. Fujimura, B. T. Zhang, K. Q. Xin, K. Okuda, C. K. Petito, C. Eisdorfer, and K. Goodkin. 1999. Independent evolution of HIV type 1 in different brain regions. AIDS Res. Hum. Retrovir. 15:811-820.[CrossRef][Medline]
    33. 33
  33. Smit, T. K., B. Wang, T. Ng, R. Osborne, B. Brew, and N. K. Saksena. 2001. Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants. Virology 279:509-526.[CrossRef][Medline]
    34. 34
  34. Staprans, S., N. Marlowe, D. Glidden, T. Novakovic-Agopian, R. M. Grant, M. Heyes, F. Aweeka, S. Deeks, and R. W. Price. 1999. Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection. AIDS 13:1051-1061.[CrossRef][Medline]
    35. 35
  35. Steuler, H., B. Storch-Hagenlocher, and B. Wildemann. 1992. Distinct populations of human immunodeficiency virus type 1 in blood and cerebrospinal fluid. AIDS Res. Hum. Retrovir. 8:53-59.[Medline]
    36. 36
  36. Tang, Y. W., J. T. Huong, R. M. Lloyd, Jr., P. Spearman, and D. W. Haas. 2000. Comparison of human immunodeficiency virus type 1 RNA sequence heterogeneity in cerebrospinal fluid and plasma. J. Clin. Microbiol. 38:4637-4639.[Abstract/Free Full Text]
    37. 37
  37. Van Marle, G., S. B. Rourke, K. Zhang, C. Silva, J. Ethier, M. J. Gill, and C. Power. 2002. HIV dementia patients exhibit reduced viral neutralization and increased envelope sequence diversity in blood and brain. AIDS 16:1905-1914.[CrossRef][Medline]
    38. 38
  38. van't Wout, A. B., L. J. Ran, C. L. Kuiken, N. A. Kootstra, S. T. Pals, and H. Schuitemaker. 1998. Analysis of the temporal relationship between human immunodeficiency virus type 1 quasispecies in sequential blood samples and various organs obtained at autopsy. J. Virol. 72:488-496.[Abstract/Free Full Text]
    39. 39
  39. Wong, J. K., C. C. Ignacio, F. Torriani, D. Havlir, N. J. Fitch, and D. D. Richman. 1997. In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues. J. Virol. 71:2059-2071.[Abstract]
    40. 40
  40. Zink, M. C., and J. E. Clements. 2002. A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease. J. Neurovirol. 8(Suppl. 2):42-48.

Journal of Virology, August 2005, p. 10830-10834, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10830-10834.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Datta, S., Panigrahi, R., Biswas, A., Chandra, P. K., Banerjee, A., Mahapatra, P. K., Panda, C. K., Chakrabarti, S., Bhattacharya, S. K., Biswas, K., Chakravarty, R. (2009). Genetic Characterization of Hepatitis B Virus in Peripheral Blood Leukocytes: Evidence for Selection and Compartmentalization of Viral Variants with the Immune Escape G145R Mutation. J. Virol. 83: 9983-9992 [Abstract] [Full Text]  
  • Ince, W. L., Harrington, P. R., Schnell, G. L., Patel-Chhabra, M., Burch, C. L., Menezes, P., Price, R. W., Eron, J. J. Jr., Swanstrom, R. I. (2009). Major Coexisting Human Immunodeficiency Virus Type 1 env Gene Subpopulations in the Peripheral Blood Are Produced by Cells with Similar Turnover Rates and Show Little Evidence of Genetic Compartmentalization. J. Virol. 83: 4068-4080 [Abstract] [Full Text]  
  • Zarate, S., Pond, S. L. K., Shapshak, P., Frost, S. D. W. (2007). Comparative Study of Methods for Detecting Sequence Compartmentalization in Human Immunodeficiency Virus Type 1. J. Virol. 81: 6643-6651 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ritola, K.
Right arrow Articles by Swanstrom, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ritola, K.
Right arrow Articles by Swanstrom, R.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»