World Journal of AIDS, 2012, 2, 226-231 Published Online September 2012 ( 223
HIV-1 Primarily Targets the Innate Immune System and
Only Secondarily Modulates Adaptive Immune Cell
Lawrence M. Agius1,2
1Department of Pathology, Mater Dei Hospital, Tal-Qroqq, Malta; 2University of Malta Medical School, Msida, Malta.
Received April 21st, 2012; revised May 14th, 2012; accepted May 25th, 2012
Persistence of HIV-1 infection allows for permissive microenvironmental conditioning in terms of contextual innate
immune participation. The progression of host cell injury constitutes an additional parametric formulation in self-am-
plifying modulation of the adaptive immune response in a manner that inclusively promotes the emergence of a final
stage of AIDS that is both depletive and permissive for opportunistic infections and various forms of neoplasia. It is
within contextual indices of promotion of depleted T-helper lymphocytes and of augmented viremic loads that manifest-
tations of classic lesions emerge as the AIDS phenomenon. It is further to be realized that an apoptotic response of mul-
tiple cell subtypes including T-lymphocytes includes host-cell participation within formulated settings of further persis-
tence of the retroviral infection. An all-inclusive phenomenon of dendritic cell-lymphocyte synapse formulation corre-
sponds to the establishment of HIV-1 infection that specifically conditions all subsequent stages in depletion of the in-
jured host cells regardless of the dynamics or kinetics of the retroviral replicative infectious process itself.
Keywords: HIV-1; Infection; Aids; Immune; Persistence
1. Introduction
HIV-1 infection is inherently a progressive disorder that
is especially productive of a chronic participation of in-
jury to CD4+ T-lymphocytes within additional contex-
tual conditioning of the AIDS phenomenon. This inher-
ently progressive infection is suggestive in itself of a
profound involvement of the innate immune system in
particular. Interferon lamba 3 activates the innate im-
mune system through the JAK-STAT pathway in macro-
phages. It inhibits HIV-1 replication in these cells and
induces many antiviral cellular factors and interferon
regulatory mediators [1]. Plasmacytoid dendritic cells
serve as an essential link between innate and adaptive
immune systems; the fate of these cells in HIV-1 infec-
tion is unclear [2]. The realization of monocyte/macro-
phage participation in the accumulation of the HIV-1
virions indicates the essential character of an infection
that arises primarily from innate immune defects. Macro-
phages and their monocyte precursors show marked het-
erogeneity and may be either proinflammatory or alter-
natively activated [3].
The ongoing development of infection to multiple he-
matopoietic cell lineages is a highly prominent feature of
injury that is ultimately the criterion for the ensuing in-
fection that is manifested primarily as acquired immune
deficiency. CNS opportunistic infections vary according
to HIV induced defects of innate immunity versus ab-
normal adaptive immunity [4].
The emergence of cellular injury therefore constitutes
the establishment of multi-lineage cellular injury that is
productive of the progressive nature to the AIDS pan-
demic. B lymphocyte abnormalities precede CD4(+) T
cell decline [5].
2. Cascade Events
The closely parallel involvement of systems of cascade
signalling in HIV-1 infected cell lines correlates espe-
cially with the recombinant HIV-1 virion variants that
establish themselves in the circulating blood of persis-
tently infected individuals. The further emergence of
highly characteristic opportunistic infections and also
especially of different forms of neoplasia are further
promotional events in the establishment of progression as
the main pathogenic mechanisms leading to the AIDS
process. Chronic immune activation appears to result
from untimely innate immune responses and is believed
to be implicated in dynamics of emergence of AIDS in
HIV-1 infected individuals [6].
Copyright © 2012 SciRes. WJA
HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion 227
Indications of non-resolution of the HIV-1 infection
arise as perpetuating involvement by a virion that is rela-
tively slowly replicative but that is capable of exquisite
evasion of the immune system. HIV-1 Nef appears im-
portant in HIV-1 transmission by dendritic cells to acti-
vated CD4(+) T cells [7]. Vpu promotes suppression of
innate immunity and counteracts natural killer cells by
interfering with CD1d expression and antigen presenta-
tion; it also suppresses expression of NK-T and B cell
antigen [8].
Recombinant variants of this retrovirus indicate the
enormous capability for adaptability to a changing mi-
croenvironment in terms of the further participation of
injury to multiple cell types. In this regard, the essential
representation of the infectious process is closely allied
to a formulated recombinatio n of multiple sero-strains as
further evidenced by subtypes of the HIV-1 virion M, O
and N, and by the subtypes of the M variant itself.
3. HIV-1 Progression
Indications of realization of HIV-1 progression appear to
arise primarily as a consequence of chemokine and cyto-
kine pathobiology as relative especially to coreceptors to
the CD4+ receptor. IL-7 effectively protects the CD4(+)
T cell pool during acute SIV infection in macaques [9].
The attributes of complicatin g neoplastic lesions in these
patients are closely formulated consequences of the pro-
longed persistence of a dual coinfection by both HIV-1
and accompanying oncogenic viruses such as human
herpes virus-8, Ebstein-Barr virus and human papilloma
virus subtypes.
In such manner, proportional accumulation of HIV-1
virions within persistently infected host cells correlates
with the emergence of depletion of the CD4+ T lympho-
cytes and of the increasing circulating viremic load.
Macrophages are essentially implicated in HIV-1 in-
fection, viral rebound and clinical emergence of AIDS
[10]. Glutathione-enhanced natural killer cells tend to
suppress mycobacterial tuberculosis infection within
human monocytes [11].
Establishment of the HIV-1 infection arises as a main
consequence of an activation phenomenon that affects
both T and B lymphocytes. In such manner, the cones-
quential attributes of recombinant subtypes of coinfect-
ing HIV-1 virions indicate a prominent derived character
for persistence towards the development of a profound
immune deficiency.
High levels of viremia in the establishment of the infec-
tious process reflect an adherence of patterned formula-
tion within pathways and cascades that include a promi-
nent paracrine microenvironmental effect. The innate
immune response appears a critical factor in initial HIV
transmission and dissemination, implicating type I inter-
feron, defensins and whey acidic proteins [16]. Enhanced
IL-2 production and improved proliferation of CD4 T
helper cells are restricted to viremic individuals. When
regulatory T cells are depleted from circulating mono-
cytes in viremic patients, IL-10 production decreases and
proinflammatory cytokines increase [17]. In this regard
the participation of multiple c ellu lar lineag es co llaborates
The latter phenomenon is itself a source for sequential
transformation of cells towards malignant neoplastic
emergence. Vpu (viral protein U) may have evolved as a
promoter of human-to-human HIV-1 transmission due to
an interplay between viral factors versus host restriction
factors [12].
4. Disease Setting
The whole setting of attributes of HIV-1 infection is con-
clusive parameter for the induction of further cellular
injury that primarily includes depletion of lymphocyte
subsets without in fact direct overwhelming infection of
such lymphocytes. In such manner, profound immune
cell depletion is a complex evolution involving by-
stander effect and also the induction of apoptosis of mul-
tiple cell-subtypes. Premature immunosenescence of the
innate immune system may be mediated by chronic en-
dotoxemia, residual viremia, telomere attrition and al-
tered cellular signallin g [13].
Inflammation is an exquisite setting for the production
of cellular injury in AIDS infections in a further contex-
tual setting of persistent HIV-1 infection. Leukotrienes
influence microglial infection and may partly control
viral load in the central nervous system [14]. It is with
regard to a multiplicity of step s in the production of new
retroviral virions that a whole panorama of adaptive
change involves an inflammatory response to the viral
infection and to the persistent process of immune defi-
ciency state leading generally to the AIDS process.
Activation of lymphocytes characterizes the early
stages of HIV-1 infection with the profound incorpora-
tion of replicative viral activity especially within mono-
cytes/macrophages. Type I interferon response by the
innate immune system is produced by plasmacytoid den-
dritic cells and appears to control HIV-1 productive in-
fection and disease progression [15].
Formulated patterns include the emergence of system-
atic processes of integration of the cDNA of the HIV-1
genome in manners that implicate insertional mutagene-
sis. The further confounding chemokine and cytokine
accompaniments by such factors as activation of the viral
reverse transcriptase indicate an overall close homology
of virion capability towards host-cell components as fur-
ther evidenced by the persistent articulation of cellular
injury to CD4+ T helper lymphocytes.
5. Viremia
Copyright © 2012 SciRes. WJA
HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion
with the involvement of multiple cell-signalin g pathways
that promote adaptive potentiality towards the host cell
that is infected. Homology of genomic components of the
virion correlates with the adoption of multiple parameters
that belie a single main pathogenic mechanism in reach-
ing establishing persisten ce of the HIV-1 infection.
6. Activation
It is in terms of adherence of host-cell response as activ-
tion mechanisms that promote a realization of cellular
injury that there is included widespread apoptosis of T
helper lymphocytes.
Correlates of a promotional nature that are mainly
characterized by a marked activation of lymphocyte sub-
sets include the formulation for further persistence of cell
injury within contextual reproduction of multiple promi-
nent lineage participations. Plasmacytoid dendritic cells
possibly enable HIV-1 elite controllers to control HIV-1
viremia [18]. Activated nervous system mononuclear
phagocytes and astrocytes expressing HIV-1 gene prod-
ucts in specific patterns may promote neurodegeneration
[19]. It is in a microenvironmentally conditioned in-
flammatory response that parameters of spread of the
HIV-1 virus include the evolution of viral resistance to
various drug treatment protocols that is commonly seen
in patients treated with anti-retroviral therapy.
Included participation of multiple cell-type infection in
HIV-1 phases of evolution allow for the development of
specific regulatory disorders that incorporate the persis-
tent infection. Intrinsic antiviral immunity tends to re-
strict infection by blocking viral replication directly in an
immediate manner [20]. Replicative activity of the retro-
virus is accompanied by a very high mutability that
self-promotes the ensuing infection as productive of the
AIDS stage of infection.
7. Aids Phase
In terms of such ongoing participation of cellular injury
in the creation of a conducive setting for persistence of
the HIV-1 infection, it is a dual involvement of inflam-
matory reactivity with the emergence of subsequent se-
vere immune deficiency that permits evolution of pat-
terns of modulated participation of such cellular injury to
lymphocyte depletion and AIDS phase establishment.
Toll-like receptors as innate immune components induce
activation of NF-kappaB that in turn promotes HIV-1
replication [21]. Humanized mice are optimal for study-
ing HIV-1 immunopathogenesis and for the development
of novel immune-based th erapies [22].
Indicative inclusion of mutability would allow for the
acquisition of a capability for pronounced depletion of
immune cells as these relate particularly to impaired ex-
pression of human histocompatibility antigens. The den-
dritic cells in particular appear a primal form of pattern ed
involvement in patients infected with HIV-1. It is in
terms of augmented activation of immune cells on the
one hand and o f impaired resolution of the cellular injury
that inflammatory microenvironmental paracrine effect
further promotes the emergence of injury to lymph nodes
and gastrointestinal associated lymphoid tissue. Fibrosis
accompanies a severely progressive lymphocytic deple-
tion in modes of further involvement of the innate im-
mune system in particular. Dendritic cells are partici-
pants in the production of spread of the HIV-1 infection
as evidenced by monocytes/macrophages that accumulate
highly replicative sites for the retrovirus.
Polymorphisms of innate immune genes affecting
Toll-like receptors and defensins modulate progression
of HIV-1 infection in children [23]. Inclusion dynamics
of the virion particles promote establishment of inte-
grated viral genomes within host-cell genomes as indi-
cated by the elaborate phases of entry and attachment to
the cell membrane, the reverse transcription of the viral
RNA genome and the formulation of transport of viral
components from the nucleus to the cytoplasm and plas-
malemma. CD4 binding site directed inhibitors (mono-
clonal antibodies) act preferentially by blocking free vi-
rus transmission while still allowing HIV-1 to spread
through cell-cell contacts [24].
The failure to recognize a single essential pathogenic
step in HIV-1 infection is symptomatic of a variety of
inducing environments that promote the production of
further attributes of the overall persistence of the viral
replication and release. The neutralizing antibody con-
stant domain functionally links innate and adaptive im-
mune systems to harness innate immune response [25].
In primary HIV-1 infection there develops dysfunction of
dendritic cells and this is independ ent of interaction with
gp120 [26].
8. Micro-Environment
Inclusive formulations of multiple component pathways
are irreducible parameters in the development of such
micro-environmental conditioning.
In such terms, inclusive forces such as pressure-in-
duced mutability of the HIV-1 genome, including such
factors as anti-retroviral drug therapy, affect the pathobi-
ologic attributes of the AIDS syndrome phase. Within a
range phenomenon of inclusive parameters, the HIV-1
infection arises largely as an integral component of the
micro-environmental milieu of inflammation and of
evolving immune deficiency. Autophagy is increasingly
being implicated in pattern recognition paradigms af-
fecting innate immunity [2 7].
TRIM5 as a restriction factor may indicate how the
innate immune system detects distinct molecular features
of HIV-1 [28].
Copyright © 2012 SciRes. WJA
HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion 229
Promotional attributes of cohesive participating roles
in such micro-environmental conditioning indicates that
HIV-1 is a privileged infectious agent that creates and
modulates multiple facets of inclusive formulation that
are directed primarily in the creation of recombinant
forms of the virion in the individual patient with AIDS. It
is further to be noted that the innate immune system in-
volvement accounts for the establishment of multiple
facets of involvement as coreceptivity as promoted by
disordered chemokine and cytokine biology. Host inva-
sion and viral replication appear orchestrated by Nef ac-
tions in macrophages including receptor expression, in-
tracellular signalling and production of mediators of in-
flamma tion [29].
Of particular relevance is the dendritic cell-lympho-
cyte/macrophage synapse in infectious modes of modu-
lated effect leading to a process of accumulation relevant
towards the ongoing persistence of the infection by
HIV-1 virus. Virological synapses between infected den-
dritic/T lymphocytes and uninfected T cells may very
well prove the do minant mode of HIV-1 spread [30]. Th e
attributes of activation of lymphocytes are clearly also a
modulation step in the evolution of the retroviral infec-
tion as an established persistence of further induction in
microenvironmental conditioning. The emergence of
multiple forms of neoplasia in the AIDS patient is sug-
gestive also of endothelial cell participation, particularly
within a setting of augmenting viremic levels that circu-
late in the peripheral blood.
9. Redistribution
An inclusively overall parameteric redistribution of the
HIV-1 virions accounts for the promotional persistence
as evidenced by a clinical setting of multiple forms of
opportunistic infection and of neoplastic lesions includ-
ing Kaposi sarcoma, non-Hodgkin lymphoma, and cer-
vical carcinoma. In such terms, implication of further
evolving pathogenesis allows a permissive environment
that conditions also the profound immune deficiency. In
effective terms, the whole integrative phenomenon of per-
sistent HIV-1 infection is a parent process of subsequent
derivative pathways of essential amplifying proportions.
Inflammasome genes are implicated in susceptibility
to HIV-1 infection [31]. The processes of derivative pa-
rameters are all-inclusive formulations that essentially
modulate the innate immune pathways as primary con-
stitutive targets of HIV-1 rather than as a primary infec-
tion of T lymphocytes per se. It is with reference to mul-
tiple inducible pathways of reproduction that macro-
phages, natural killer cells and dendritic cells promote a
setting of modulated permissiveness that contributes di-
rectly to the establishment of the persistent nature of the
HIV-1 infection. Strong antibody mediated activation of
Natural Killer cells to HIV-1 Env occurs in persistent
HIV-1 infection [32].
Apoptosis may be viewed as an essential reflection of
such amplifying microenvironmental conditioning with
regard to secondary acquisition of the T helper lympho-
cyte depletion.
Activation of both T and B lymphocytes appears a
correlative phenomenon in itself that demarcates potenti-
ality for persistence of the retroviral infection. A promo-
tional accumulative viral load empowers the emergence
of persistent viral infection, regardless of the degree of
viral particle replication within specific cellular or im-
mune cellular subsets. HIV-1 is able to productively in-
fect nondividing cells as well as dividing cells at inter-
phase by actively delivering its DNA into the nucleus by
means of ho st nuclear impor t machine ry [33].
Replicative activity of host cells correlates with viral
replication formulas and promotes the microenviron-
mental conditioning that harbors further potential non-
resolution of cell injury of virally infected host cells.
Redistribution of lymphocytes and also of other cell-
types such as dendritic cells promotes a systemically
promotional effect to HIV-1 infection as also noted with
regard to the AIDS phase of infection.
10. Concluding Remarks
Parameters of induction and non-resolution of HIV-1
infection indicate an exquisite acquisition of a self-am-
plifying range of potentialities th at specifically indicate a
primary all-embracing involvement of the innate immune
system; this responds by implicating in secondary fash-
ion a pathobiologic activation of the adaptive immune
Further evolution of the retroviral infection imposes
pressure effects on multiple cell subtypes in a manner
that implicates cytokine and chemokine modulation
within a microenvironmental inflammatory milieu. The
apoptosis of host cells is sharply distin ct from a dynamo-
ics that solely targets such cells as replicative reservoirs
of the HIV-1; this phenomenon is suggestive of a modu-
lation that is specifically both an activating and dep letive
inclusive formulation of viremic and host-cell co-infec-
A systemic redistribution of host cell injury evolves
within a contextual representation of multiple cell sub-
types ranging from macrophages, dendritic cells, natural
killer cells to endothelial cells in inducing persistence of
the infection as the one paramount dynamics of HIV-1
involvement of the individual patient progressing to
AIDS as a distinct disease phase.
[1] M. Q. Liu, D. J. Zhou , X. Wang , W. Zhou , L. Ye and J.
Copyright © 2012 SciRes. WJA
HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion
L. Li, “IFN-Lambda3 Inhibits HIV Infection of Macro-
phages through the JAK-STAT Pathway,” PloS One, Vol.
7, No. 4, 2012, Article ID: e35902.
[2] M. L. Gougeon and J. P. Herbeuval, “IFN-ALPHA and
TRAIL: A Double Edge Sword in HIV-1 Disease?” Ex-
perimental Cell Research, Vol. 318, No. 11, 2012, pp.
1260-1268. doi:10.1016/j.yexcr.2012.03.012
[3] L. Cassetta, E. Cassol and G. Poli, “Macrophage Polari-
zation in Health and Disease,” Scientific World Journal,
Vol. 11, 2011, pp. 2391-2402. doi:10.1100/2011/213962
[4] A. Nath and J. R. Berger, “Complications of Immunosup-
pressive/Immunomodulatory Therapy in Neurological
Diseases,” Current Treatment Options in Neurology, Vol.
14, No. 3, 2012, pp. 241-255.
[5] M. Fogil, C. Toiti, F. Malacarne, S. Florentini, M. Albani
and I. Izzo, “Emergence of Exhausted B Cells in Asy-
mptomatic HIV-1 Infected Patients Naïve for HAART Is
Related to Reduced Immune Surveillance,” Clinical and
Developmental Immunology, 2012, in Press.
[6] A. Benecke, M. Gale Jr. and M. G. Katze, “Dynamics of
Innate Immunity Are Key to Chronic Immune Activation
in AIDS,” Current Opinion in HIV and AIDS, Vol. 7, No.
1, 2012, pp. 79-85. doi:10.1097/COH.0b013e32834dde31
[7] C. St. Gelais, C. M. Coleman, J. H. Wang and L. Wu,
“HIV-1 Nef Enhances Dendritic Cell-Mediated Viral
Transmission to CD4(+) T Cells and Promotes T-Cell
Activation,” PLoS One, Vol. 7, No. 3, 2012, Article ID:
e34521. doi:10.1371/journal.pone.0034521
[8] J. K. Sandberg, S. K. Andersson, S. M. Bachle, D. F.
Nixon and M. Moll, “HIV-1 Vpu Interference with Innate
Cell-Mediated Immune Mechanisms,” Current HIV Re-
search, 2012, in Press.
[9] L. Vassena, H. Miao, R. Cibro, M. S. Mainati, G. Cassina
and M. A. Proschan, “Treatment with IL-7 Prevents the
Decline of Circulating CD4 (+) T Cells during the Acute
Phase of SIV Infection in Rhesus Macaques,” PLoS
Pathogens, Vol. 8, No. 4, 2012, Article ID: e1002636.
[10] J. E. Hazleton, J. W. Berman and E. A. Eugenin, “P uri ne r-
gic Receptors Are Required for HIV-1 Infection of Pri-
mary Human Macrophages,” Journal of Immunology,
[11] C. Guerra, K. Johal, D. Morris, S. Moreno, O. Alvarado
and D. Gray, “Control of Mycobacterium Tuberculosis
Growth by Activated Natural Killer Cells,” Clinical &
Experimental Immunology, Vol. 168, No. 1, 2012, pp.
142-152. doi:10.1111/j.1365-2249.2011.04552.x
[12] K. Sato, P. Gee and Y. Koyanagi, “Vpu and BST2: Still
Not There Yet?” Frontiers in Microbiology, Vol. 3, No.
131, 2012.
[13] A. C. Hearps, T. A. Angelovich, A. Jaworowski, J. Mills,
A. L. Landay and S. M. Crowe, “HIV Infection and Ag-
ing of the Innate Immune System,” Sex Health, Vol. 8,
No. 4, 2011, pp. 453-464. doi:10.1071/SH11028
[14] J. Bertin, C. Baret, D. Belanger and M. J. Tremblay,
“Leukotrienes Inhibit Early Stages of HIV-1 Infection in
Monocyte-Derived Microglia-Like Cells,” Journal of
Neuroinflammation, Vol. 9, No. 1, 2012, p. 55.
[15] R. Hughes, G. Towers and M. Noursadeghi, “Innate Im-
mune Interferon Responses to Human Immunodeficiency
Virus-1 Infection,” Reviews in Medical Virology, Vol. 22,
No. 4, 2012, pp. 257-266. doi:10.1002/rmv.1708
[16] J. L. Reading, A. F. Meyers and A. Vyakarnam, “Whey
Acidic Proteins (WAPs): Novel Modulators of Innate
Immunity to HIV Infection,” Current Opinion in HIV and
AIDS, Vol. 7, No. 2, 2012, pp. 172-179.
[17] D. S. Kwon, M. Augin, T. Hongo, K. M. Law, J. Johnson
and F. Porichis “CD4+ CD25+ Regulatory T Cells Impair
HIV-Specific CD4 T Cell Responses by Upregulating
IL-10 Production in Monocytes,” Journal of Virology,
2012. doi:10.1128/JVI.06251-11
[18] K. Machmach, M. Leal, C. Gras, P. Viciana, M. Geneba
and E. Franco, “Plasmacytoid Dendritic Cells Reduce
HIV Production in Elite Controllers,” Journal of Virology,
Vol. 86, No. 8, 2012, pp. 4245-4252.
[19] W. Royal III, L. Zhang, M. Guo, O. Jones, H. Davis and J.
L. Bryant, “Immune Activation, Viral Gene Product Ex-
pression and Neurotoxicity in the HIV-1 Transgenic Rat,”
Journal of Neuroimmunology, Vol. 247, No. 1, 2012, pp.
16-24. doi:10.1016/j.jneuroim.2012.03.015
[20] N. Yan and Z. J. Chen, “Intrinsic Antiviral Immunity,”
Nature Immunology, Vol. 13, No. 3, 2012, pp. 214-222.
[21] J. C. Hernandez, M. Stevenson, E. Latz and S. Urcuqui-
Inchima, “HIV Type 1 Infection Up-Regulates TLR-2 and
TLR-4 Expression and Function in Vivo and in Vitro,”
AIDS Research and Human Retroviruses, 2012.
[22] L. Zhang and L. Su, “HIV-1 Immunopathogenesis in
Humanized Mouse Models,” Cellular & Molecular Im-
munology, 2012. doi:10.1038/cmi.2012.7
[23] R. Freguja, K. Glanesin, P. Del Bianco, S. Malacrida, O.
Rampon and M. Zanchetta, “Polymorphisms of Innate
Immunity Genes Influence Disease Progression in HIV-1
Infected Children,” AIDS, Vol. 26, No. 6, 2012, pp. 765-
768. doi:10.1097/QAD.0b013e3283514350
[24] I. A. Abela, L. Berlinger, M. Schanz, L. Reynell, H. F.
Gunthard and P. Rusert, “Cell-Cell Transmission Enables
HIV-1 to Evade Inhibition by Potent CD4bs Directed An-
tibodies,” PLoS Pathogens, Vol. 8, No. 4, 2012, Article
ID: e1002634. doi:10.1371/journal.ppat.1002634
[25] M. E. Ackerman, A. S. Dugast and G. Alter, “Emerging
Concepts on the Role of Innate Immunity in the Preven-
tion and Control of HIV Infection,” Annual Review of
Medicine, Vol. 63, 2012, pp. 113-130.
[26] J. Vani, S. V. Kaveri and J. Bayry, “Myeloid Dendritic
Cell Dysfunction during Primary HIV-1 Infection Is In-
dependent of Interaction with gp120,” Journal of Infec-
tious Diseases, 2012. doi:10.1093/infdis/jis292
[27] V. Deretic, “Autophagy as an Innate Immunity Paradigm:
Expanding the Scope and Repertoire of Pattern Recogni-
Copyright © 2012 SciRes. WJA
HIV-1 Primarily Targets the Innate Immune System and Only Secondarily Modulates Adaptive Immune Cell Depletion
Copyright © 2012 SciRes. WJA
tion Receptors,” Current Opinion in Immunology, Vol. 24,
No. 1, 2012, pp. 21-31.
[28] M. G. Grutter and J. Luban, “TRIM5 Structure, HIV-1
Capsid Recognition, and Innate Immune Signalling,”
Current Opinion in Virology, Vol. 2, No. 2, 2012, pp.
142-150. doi:10.1016/j.coviro.2012.02.003
[29] Y. Ghiglione and G. Turk, “Nef Performance in Macro-
phages: The Master Orchestrator of Viral Persistence and
Spread,” Current HIV Research, Vol. 9, No. 7, 2011, pp.
505-513. doi:10.2174/157016211798842080
[30] B. K. Chen, “T Cell Virological Synapses and HIV-1
Pathogenesis,” Immunology Research, 2012, in Press.
[31] A. Pontillo, T. M. Oshiro, M. Girardelli, A. J. Kamada, S.
Crovella and A. J. Duarte, “Polymorphisms in Inflam-
masome Genes and Susceptibility to HIV-1 Infection,”
Journal of Acquired Immune Deficiency Syndromes, Vol.
59, No. 2, 2012, pp. 121-125.
[32] C. F. Thobakgale, L. Fadda, K. Lane, I. Toth, F. Pereyra
and S. Bazner, “Frequent and Strong Antibody-Mediated
Natural Killer C Activation to HIV Env in Individuals
with Chronic HIV-1 Infection,” Journal of Virology, 2012,
in Press. doi:10.1128/JVI.00569-12
[33] K. D. Jayappa, Z. Ao and X. Yao, “The HIV-1 Passage
from Cytoplasm to Nucleus: The Process Involving a
Complex Exchange between the Components of HIV-1
and Cellular Machinery to Access Nuclear and Successful
Integration,” International Journal of Biochemistry and
Molecular Bi ology, Vol. 3, No. 1, 2012, pp. 70-85.